Variant 12-64042931-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020762.4(SRGAP1):c.631C>T(p.Arg211Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0003 in 1,613,382 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 2 hom. )

Consequence

SRGAP1
NM_020762.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.796

Variant links:

Genes affected

SRGAP1 (HGNC:17382): (SLIT-ROBO Rho GTPase activating protein 1) The protein encoded by this gene is a GTPase activator, working with the GTPase CDC42 to negatively regulate neuronal migration. The encoded protein interacts with the transmembrane receptor ROBO1 to inactivate CDC42. [provided by RefSeq, Sep 2016]

SRGAP1 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SRGAP1	NM_020762.4 linkuse as main transcript	c.631C>T	p.Arg211Trp	missense_variant	5/22	ENST00000355086.8
SRGAP1	NM_001346201.2 linkuse as main transcript	c.631C>T	p.Arg211Trp	missense_variant	5/22
SRGAP1	XM_024449096.2 linkuse as main transcript	c.631C>T	p.Arg211Trp	missense_variant	5/14
SRGAP1	XM_024449097.2 linkuse as main transcript	c.631C>T	p.Arg211Trp	missense_variant	5/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRGAP1	ENST00000355086.8 linkuse as main transcript	c.631C>T	p.Arg211Trp	missense_variant	5/22	1	NM_020762.4	A1	Q7Z6B7-1
	ENST00000535594.1 linkuse as main transcript	n.143G>A		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000188

AC:

AN:

250220

Hom.:

AF XY:

0.000207

AC XY:

AN XY:

135220

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000354

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000314

AC:

459

AN:

1461342

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

235

AN XY:

726998

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000378

Gnomad4 OTH exome

AF:

0.000249

GnomAD4 genome

AF:

0.000164

AC:

AN:

152040

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000252

Hom.:

Bravo

AF:

0.000227

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000189

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000356

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

Nov 16, 2021

The c.631C>T (p.R211W) alteration is located in exon 5 (coding exon 5) of the SRGAP1 gene. This alteration results from a C to T substitution at nucleotide position 631, causing the arginine (R) at amino acid position 211 to be replaced by a tryptophan (W). 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

0.83

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Uncertain

-0.070

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.43

T;T;T

Eigen

Benign

0.17

Eigen_PC

Benign

0.065

FATHMM_MKL

Uncertain

0.83

LIST_S2

Pathogenic

1.0

D;D;.

M_CAP

Uncertain

0.18

MetaRNN

Uncertain

0.69

D;D;D

MetaSVM

Uncertain

-0.27

MutationAssessor

Uncertain

2.7

M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-6.7

D;.;D

REVEL

Uncertain

0.34

Sift

Pathogenic

0.0

D;.;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.70

MVP

0.56

MPC

0.86

ClinPred

0.37

GERP RS

2.2

Varity_R

0.41

gMVP

0.55

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