Variant 7-16462930-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015464.3(SOSTDC1):c.239C>G(p.Ser80Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,437,220 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SOSTDC1
NM_015464.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

Variant links:

Genes affected

SOSTDC1 (HGNC:21748): (sclerostin domain containing 1) This gene is a member of the sclerostin family and encodes an N-glycosylated, secreted protein with a C-terminal cystine knot-like domain. This protein functions as a bone morphogenetic protein (BMP) antagonist. Specifically, it directly associates with BMPs, prohibiting them from binding their receptors, thereby regulating BMP signaling during cellular proliferation, differentiation, and programmed cell death. [provided by RefSeq, Jul 2008]

SOSTDC1 links:

LOC105375168 (HGNC:):

LOC105375168 links:

CRPPA (HGNC:37276): (CDP-L-ribitol pyrophosphorylase A) This gene encodes a 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase-like protein. Mutations in this gene are the cause of Walker-Warburg syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

CRPPA links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SOSTDC1	NM_015464.3 linkuse as main transcript	c.239C>G	p.Ser80Cys	missense_variant	2/2	ENST00000307068.5
LOC105375168	XR_007060223.1 linkuse as main transcript	n.581-7690G>C		intron_variant, non_coding_transcript_variant
LOC105375168	XR_007060220.1 linkuse as main transcript	n.736+1614G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOSTDC1	ENST00000307068.5 linkuse as main transcript	c.239C>G	p.Ser80Cys	missense_variant	2/2	1	NM_015464.3	P1	Q6X4U4-1
SOSTDC1	ENST00000396652.1 linkuse as main transcript	c.311C>G	p.Ser104Cys	missense_variant	5/5	2			Q6X4U4-2
CRPPA	ENST00000674759.1 linkuse as main transcript	c.-47+33450C>G		intron_variant
CRPPA	ENST00000675257.1 linkuse as main transcript	c.-47+33450C>G		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1437220

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710354

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:

0.00000183

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2021

The c.239C>G (p.S80C) alteration is located in exon 2 (coding exon 2) of the SOSTDC1 gene. This alteration results from a C to G substitution at nucleotide position 239, causing the serine (S) at amino acid position 80 to be replaced by a cysteine (C). 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

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.91

D;.

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.96

D;D

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Uncertain

0.30

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.3

D;D

REVEL

Pathogenic

0.66

Sift

Benign

0.068

T;T

Sift4G

Benign

0.067

T;T

Polyphen

1.0

D;.

Vest4

0.79

MutPred

0.55

Gain of sheet (P = 0.0221);.;

MVP

0.86

MPC

0.90

ClinPred

0.99

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.43

gMVP

0.73

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