7-16462765-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015464.3(SOSTDC1):c.404A>G(p.Asn135Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,614,196 control chromosomes in the GnomAD database, including 165 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 12 hom., cov: 32)

Exomes 𝑓: 0.013 ( 153 hom. )

Consequence

SOSTDC1
NM_015464.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.32

Publications

11 publications found

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:

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 Gene-Disease associations (from GenCC):

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
myopathy caused by variation in CRPPA
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive limb-girdle muscular dystrophy type 2U
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
congenital muscular dystrophy without intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
muscular dystrophy-dystroglycanopathy, type A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CRPPA links:

ENSG00000272537 (HGNC:):

ENSG00000272537 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008537382).

BP6

Variant 7-16462765-T-C is Benign according to our data. Variant chr7-16462765-T-C is described in ClinVar as [Benign]. Clinvar id is 2657327.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 1563 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOSTDC1	NM_015464.3 link	c.404A>G	p.Asn135Ser	missense_variant	Exon 2 of 2	ENST00000307068.5	NP_056279.1	Q6X4U4-1A4D125
LOC105375168	XR_007060220.1 link	n.736+1449T>C		intron_variant	Intron 5 of 5
LOC105375168	XR_007060223.1 link	n.581-7855T>C		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOSTDC1	ENST00000307068.5 link	c.404A>G	p.Asn135Ser	missense_variant	Exon 2 of 2	1	NM_015464.3	ENSP00000304930.4		Q6X4U4-1

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1564

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00263

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.00968

Gnomad ASJ

AF:

0.0303

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00621

Gnomad FIN

AF:

0.00631

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0152

Gnomad OTH

AF:

0.0120

GnomAD2 exomes

AF:

0.0104

AC:

2620

AN:

251318

AF XY:

0.0112

show subpopulations

Gnomad AFR exome

AF:

0.00277

Gnomad AMR exome

AF:

0.00726

Gnomad ASJ exome

AF:

0.0255

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00661

Gnomad NFE exome

AF:

0.0148

Gnomad OTH exome

AF:

0.0126

GnomAD4 exome

AF:

0.0128

AC:

18643

AN:

1461888

Hom.:

153

Cov.:

AF XY:

0.0127

AC XY:

9241

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00245

AC:

AN:

33480

American (AMR)

AF:

0.00789

AC:

353

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0271

AC:

708

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00569

AC:

491

AN:

86258

European-Finnish (FIN)

AF:

0.00605

AC:

323

AN:

53418

Middle Eastern (MID)

AF:

0.0135

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0142

AC:

15789

AN:

1112008

Other (OTH)

AF:

0.0135

AC:

818

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1167

2334

3502

4669

5836

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0103

AC:

1563

AN:

152308

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

753

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00262

AC:

109

AN:

41562

American (AMR)

AF:

0.00961

AC:

147

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0303

AC:

105

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00621

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00631

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0152

AC:

1034

AN:

68020

Other (OTH)

AF:

0.0118

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

182

273

364

455

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0131

Hom.:

Bravo

AF:

0.0106

TwinsUK

AF:

0.0221

AC:

ALSPAC

AF:

0.0119

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0164

AC:

141

ExAC

AF:

0.0100

AC:

1214

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0167

EpiControl

AF:

0.0186

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CRPPA: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.59

D;.

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.95

D;D

MetaRNN

Benign

0.0085

T;T

MetaSVM

Benign

-0.33

MutationAssessor

Benign

2.0

M;.

PhyloP100

3.3

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.4

N;N

REVEL

Uncertain

0.34

Sift

Benign

0.68

T;T

Sift4G

Benign

0.70

T;T

Polyphen

0.85

P;.

Vest4

0.42

MPC

0.39

ClinPred

0.029

GERP RS

5.7

Varity_R

0.20

gMVP

0.58

Mutation Taster

=95/5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

7-16462765-T-C

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