Variant 2-20204094-C-T 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_002997.5(SDC1):c.346G>A(p.Ala116Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000963 in 1,609,082 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 6 hom., cov: 31)

Exomes 𝑓: 0.00063 ( 3 hom. )

Consequence

SDC1
NM_002997.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.698

Variant links:

Genes affected

SDC1 (HGNC:10658): (syndecan 1) The protein encoded by this gene is a transmembrane (type I) heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family. The syndecans mediate cell binding, cell signaling, and cytoskeletal organization and syndecan receptors are required for internalization of the HIV-1 tat protein. The syndecan-1 protein functions as an integral membrane protein and participates in cell proliferation, cell migration and cell-matrix interactions via its receptor for extracellular matrix proteins. Altered syndecan-1 expression has been detected in several different tumor types. While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same protein. [provided by RefSeq, Jul 2008]

SDC1 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=0.0035687387).

BP6

Variant 2-20204094-C-T is Benign according to our data. Variant chr2-20204094-C-T is described in ClinVar as [Benign]. Clinvar id is 742271.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 631 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDC1	NM_002997.5 linkuse as main transcript	c.346G>A	p.Ala116Thr	missense_variant	3/5	ENST00000254351.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDC1	ENST00000254351.9 linkuse as main transcript	c.346G>A	p.Ala116Thr	missense_variant	3/5	1	NM_002997.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00407

AC:

618

AN:

151928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0132

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00256

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00139

AC:

343

AN:

247426

Hom.:

AF XY:

0.00111

AC XY:

149

AN XY:

134088

show subpopulations

Gnomad AFR exome

AF:

0.0132

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00638

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.000630

AC:

918

AN:

1457036

Hom.:

Cov.:

AF XY:

0.000549

AC XY:

398

AN XY:

725028

show subpopulations

Gnomad4 AFR exome

AF:

0.0150

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.00586

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000409

Gnomad4 NFE exome

AF:

0.0000890

Gnomad4 OTH exome

AF:

0.00169

GnomAD4 genome

AF:

0.00415

AC:

631

AN:

152046

Hom.:

Cov.:

AF XY:

0.00422

AC XY:

314

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0135

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00100

Hom.:

Bravo

AF:

0.00443

ESP6500AA

AF:

0.00794

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00125

AC:

152

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

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

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.95

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

T;T;.;.

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.55

.;T;T;T

MetaRNN

Benign

0.0036

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.83

L;L;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

0.060

N;N;N;N

REVEL

Benign

0.018

Sift

Benign

0.37

T;T;T;T

Sift4G

Benign

0.88

T;T;T;.

Polyphen

0.016

B;B;B;.

Vest4

0.025

MVP

0.36

MPC

0.24

ClinPred

0.0044

GERP RS

-0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.035

gMVP

0.12

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