NM_015330.6:c.562C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_015330.6(SPECC1L):c.562C>T(p.Leu188Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00654 in 1,614,182 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 10 hom., cov: 33)

Exomes 𝑓: 0.0064 ( 61 hom. )

Consequence

SPECC1L
NM_015330.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.34

Publications

10 publications found

Variant links:

Genes affected

SPECC1L (HGNC:29022): (sperm antigen with calponin homology and coiled-coil domains 1 like) This gene encodes a coiled-coil domain containing protein. The encoded protein may play a critical role in actin-cytoskeletal reorganization during facial morphogenesis. Mutations in this gene are a cause of oblique facial clefting-1. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. A read-through transcript composed of SPECC1L (sperm antigen with calponin homology and coiled-coil domains 1-like) and the downstream ADORA2A (adenosine A2a receptor) gene sequence has been identified, but it is thought to be non-coding. [provided by RefSeq, Jun 2013]

SPECC1L links:

SPECC1L-ADORA2A (HGNC:49185): (SPECC1L-ADORA2A readthrough (NMD candidate)) This locus represents naturally occurring readthrough transcription between the neighboring SPECC1L (sperm antigen with calponin homology and coiled-coil domains 1-like) and ADORA2A (adenosine A2a receptor) genes on chromosome 22. The readthrough transcript is a candidate for nonsense-mediated mRNA decay (NMD) and is unlikely to produce a protein product. [provided by RefSeq, Jun 2013]

SPECC1L-ADORA2A links:

ENSG00000299949 (HGNC:):

ENSG00000299949 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059348345).

BP6

Variant 22-24321542-C-T is Benign according to our data. Variant chr22-24321542-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1134 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPECC1L	NM_015330.6 link	c.562C>T	p.Leu188Phe	missense_variant	Exon 5 of 17	ENST00000314328.14	NP_056145.5	Q69YQ0-1B2RMV2
SPECC1L	NM_001145468.4 link	c.562C>T	p.Leu188Phe	missense_variant	Exon 4 of 16		NP_001138940.4	B2RMV2
SPECC1L	NM_001254732.3 link	c.562C>T	p.Leu188Phe	missense_variant	Exon 4 of 15		NP_001241661.3	Q69YQ0-2
SPECC1L-ADORA2A	NR_103546.1 link	n.870C>T		non_coding_transcript_exon_variant	Exon 5 of 20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPECC1L	ENST00000314328.14 link	c.562C>T	p.Leu188Phe	missense_variant	Exon 5 of 17	1	NM_015330.6	ENSP00000325785.8		Q69YQ0-1
SPECC1L-ADORA2A	ENST00000358654.2 link	n.562C>T		non_coding_transcript_exon_variant	Exon 5 of 20	2		ENSP00000351480.2		F8WAN1

Frequencies

GnomAD3 genomes

AF:

0.00745

AC:

1134

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.00850

Gnomad ASJ

AF:

0.00836

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0308

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00807

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.00767

AC:

1930

AN:

251468

AF XY:

0.00781

show subpopulations

Gnomad AFR exome

AF:

0.000861

Gnomad AMR exome

AF:

0.00408

Gnomad ASJ exome

AF:

0.0106

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0294

Gnomad NFE exome

AF:

0.00819

Gnomad OTH exome

AF:

0.00961

GnomAD4 exome

AF:

0.00644

AC:

9415

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00642

AC XY:

4667

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.000836

AC:

AN:

33480

American (AMR)

AF:

0.00443

AC:

198

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00884

AC:

231

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00143

AC:

123

AN:

86256

European-Finnish (FIN)

AF:

0.0265

AC:

1417

AN:

53390

Middle Eastern (MID)

AF:

0.0140

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00626

AC:

6963

AN:

1112010

Other (OTH)

AF:

0.00619

AC:

374

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

648

1295

1943

2590

3238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

216

432

648

864

1080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00744

AC:

1134

AN:

152322

Hom.:

Cov.:

AF XY:

0.00836

AC XY:

623

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000938

AC:

AN:

41570

American (AMR)

AF:

0.00849

AC:

130

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00836

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00124

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0308

AC:

327

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00807

AC:

549

AN:

68028

Other (OTH)

AF:

0.0113

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

125

187

250

312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0107

Hom.:

761

Bravo

AF:

0.00587

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00802

AC:

ExAC

AF:

0.00723

AC:

878

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00889

EpiControl

AF:

0.00830

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SPECC1L: BS2 -

Aug 29, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oculomaxillofacial dysostosis;CN306405:Teebi hypertelorism syndrome 1

Benign:1

Apr 25, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Pathogenic

0.22

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Uncertain

0.92

LIST_S2

Pathogenic

0.98

.;D;.;.;D

MetaRNN

Benign

0.0059

T;T;T;T;T

MetaSVM

Uncertain

0.038

PhyloP100

3.3

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-2.0

N;N;N;N;D

REVEL

Benign

0.25

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D

Vest4

0.75

MVP

0.72

MPC

1.3

ClinPred

0.017

GERP RS

5.6

gMVP

0.43

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over