rs3747113

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015330.6(SPECC1L):c.570G>A(p.Thr190Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,613,942 control chromosomes in the GnomAD database, including 53,073 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4154 hom., cov: 33)

Exomes 𝑓: 0.26 ( 48919 hom. )

Consequence

SPECC1L
NM_015330.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -3.42

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 22-24321550-G-A is Benign according to our data. Variant chr22-24321550-G-A is described in ClinVar as [Benign]. Clinvar id is 1282641.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-24321550-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.42 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPECC1L	NM_015330.6 link	c.570G>A	p.Thr190Thr	synonymous_variant	Exon 5 of 17	ENST00000314328.14	NP_056145.5	Q69YQ0-1B2RMV2
SPECC1L	NM_001145468.4 link	c.570G>A	p.Thr190Thr	synonymous_variant	Exon 4 of 16		NP_001138940.4	B2RMV2
SPECC1L	NM_001254732.3 link	c.570G>A	p.Thr190Thr	synonymous_variant	Exon 4 of 15		NP_001241661.3	Q69YQ0-2
SPECC1L-ADORA2A	NR_103546.1 link	n.878G>A		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.570G>A	p.Thr190Thr	synonymous_variant	Exon 5 of 17	1	NM_015330.6	ENSP00000325785.8		Q69YQ0-1
SPECC1L-ADORA2A	ENST00000358654.2 link	n.570G>A		non_coding_transcript_exon_variant	Exon 5 of 20	2		ENSP00000351480.2		F8WAN1

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34189

AN:

152028

Hom.:

4150

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.233

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.173

Gnomad FIN

AF:

0.252

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.233

GnomAD3 exomes

AF:

0.245

AC:

61636

AN:

251396

Hom.:

8016

AF XY:

0.242

AC XY:

32897

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.324

Gnomad ASJ exome

AF:

0.234

Gnomad EAS exome

AF:

0.226

Gnomad SAS exome

AF:

0.180

Gnomad FIN exome

AF:

0.243

Gnomad NFE exome

AF:

0.258

Gnomad OTH exome

AF:

0.257

GnomAD4 exome

AF:

0.256

AC:

374357

AN:

1461796

Hom.:

48919

Cov.:

AF XY:

0.253

AC XY:

184208

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.327

Gnomad4 ASJ exome

AF:

0.238

Gnomad4 EAS exome

AF:

0.268

Gnomad4 SAS exome

AF:

0.181

Gnomad4 FIN exome

AF:

0.243

Gnomad4 NFE exome

AF:

0.264

Gnomad4 OTH exome

AF:

0.250

GnomAD4 genome

AF:

0.225

AC:

34219

AN:

152146

Hom.:

4154

Cov.:

AF XY:

0.226

AC XY:

16777

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.137

Gnomad4 AMR

AF:

0.291

Gnomad4 ASJ

AF:

0.233

Gnomad4 EAS

AF:

0.232

Gnomad4 SAS

AF:

0.172

Gnomad4 FIN

AF:

0.252

Gnomad4 NFE

AF:

0.263

Gnomad4 OTH

AF:

0.237

Alfa

AF:

0.254

Hom.:

6945

Bravo

AF:

0.226

Asia WGS

AF:

0.222

AC:

773

AN:

3478

EpiCase

AF:

0.260

EpiControl

AF:

0.260

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 12, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Teebi hypertelorism syndrome

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal dominant Opitz G/BBB syndrome

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oculomaxillofacial dysostosis

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.38

DANN

Benign

0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over