Variant chr22-24313389-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong

The NM_015330.6(SPECC1L):c.230G>A(p.Ser77Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SPECC1L
NM_015330.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33

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:):

SPECC1L-ADORA2A links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SPECC1L. . Gene score misZ 1.5985 (greater than the threshold 3.09). Trascript score misZ 3.1934 (greater than threshold 3.09). GenCC has associacion of gene with autosomal dominant Opitz G/BBB syndrome, hypertelorism, Teebi type, commissural facial cleft, Tessier number 4 facial cleft.

BP4

Computational evidence support a benign effect (MetaRNN=0.049943298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SPECC1L	NM_015330.6 linkuse as main transcript	c.230G>A	p.Ser77Asn	missense_variant	4/17	ENST00000314328.14
SPECC1L-ADORA2A	NR_103546.1 linkuse as main transcript	n.538G>A		non_coding_transcript_exon_variant	4/20
SPECC1L	NM_001145468.4 linkuse as main transcript	c.230G>A	p.Ser77Asn	missense_variant	3/16
SPECC1L	NM_001254732.3 linkuse as main transcript	c.230G>A	p.Ser77Asn	missense_variant	3/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPECC1L	ENST00000314328.14 linkuse as main transcript	c.230G>A	p.Ser77Asn	missense_variant	4/17	1	NM_015330.6	P1	Q69YQ0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 14, 2023

The c.230G>A (p.S77N) alteration is located in exon 4 (coding exon 2) of the SPECC1L gene. This alteration results from a G to A substitution at nucleotide position 230, causing the serine (S) at amino acid position 77 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.91

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.75

.;T;.;.;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.050

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.90

D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.19

N;N;N;N;N

REVEL

Benign

0.069

Sift

Benign

0.43

T;T;T;T;T

Sift4G

Benign

0.39

T;T;T;T;T

Vest4

0.089

MutPred

0.15

Loss of glycosylation at S77 (P = 0.002);Loss of glycosylation at S77 (P = 0.002);Loss of glycosylation at S77 (P = 0.002);Loss of glycosylation at S77 (P = 0.002);.;

MVP

0.33

MPC

0.36

ClinPred

0.078

GERP RS

-1.7

gMVP

0.062

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over