Variant chr7-16462765-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE
SOSTDC1	NM_015464.3 linkuse as main transcript	c.404A>G	p.Asn135Ser	missense_variant	2/2	ENST00000307068.5
LOC105375168	XR_007060223.1 linkuse as main transcript	n.581-7855T>C		intron_variant, non_coding_transcript_variant
LOC105375168	XR_007060220.1 linkuse as main transcript	n.736+1449T>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.404A>G	p.Asn135Ser	missense_variant	2/2	1	NM_015464.3	P1	Q6X4U4-1
SOSTDC1	ENST00000396652.1 linkuse as main transcript	c.476A>G	p.Asn159Ser	missense_variant	5/5	2			Q6X4U4-2
CRPPA	ENST00000674759.1 linkuse as main transcript	c.-47+33615A>G		intron_variant
CRPPA	ENST00000675257.1 linkuse as main transcript	c.-47+33615A>G		intron_variant

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

GnomAD3 exomes

AF:

0.0104

AC:

2620

AN:

251318

Hom.:

AF XY:

0.0112

AC XY:

1516

AN XY:

135816

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 SAS exome

AF:

0.00552

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

Gnomad4 AFR exome

AF:

0.00245

Gnomad4 AMR exome

AF:

0.00789

Gnomad4 ASJ exome

AF:

0.0271

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00569

Gnomad4 FIN exome

AF:

0.00605

Gnomad4 NFE exome

AF:

0.0142

Gnomad4 OTH exome

AF:

0.0135

GnomAD4 genome

AF:

0.0103

AC:

1563

AN:

152308

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

753

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00262

Gnomad4 AMR

AF:

0.00961

Gnomad4 ASJ

AF:

0.0303

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00621

Gnomad4 FIN

AF:

0.00631

Gnomad4 NFE

AF:

0.0152

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0142

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

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

CRPPA: BS1, BS2; SOSTDC1: 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

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;.

MutationTaster

Benign

1.0

D;D

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

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