Variant 3-8990718-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014850.4(SRGAP3):c.2680A>G(p.Ser894Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000897 in 1,611,726 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 7 hom., cov: 33)

Exomes 𝑓: 0.00049 ( 7 hom. )

Consequence

SRGAP3
NM_014850.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.88

Variant links:

Genes affected

SRGAP3 (HGNC:19744): (SLIT-ROBO Rho GTPase activating protein 3) Predicted to enable GTPase activator activity. Predicted to be involved in negative regulation of cell migration. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SRGAP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051725805).

BP6

Variant 3-8990718-T-C is Benign according to our data. Variant chr3-8990718-T-C is described in ClinVar as [Benign]. Clinvar id is 729048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00482 (734/152294) while in subpopulation AFR AF= 0.0163 (677/41584). AF 95% confidence interval is 0.0153. There are 7 homozygotes in gnomad4. There are 361 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 734 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRGAP3	NM_014850.4 linkuse as main transcript	c.2680A>G	p.Ser894Gly	missense_variant	21/22	ENST00000383836.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRGAP3	ENST00000383836.8 linkuse as main transcript	c.2680A>G	p.Ser894Gly	missense_variant	21/22	1	NM_014850.4	P1	O43295-1
SRGAP3	ENST00000360413.7 linkuse as main transcript	c.2608A>G	p.Ser870Gly	missense_variant	21/22	1			O43295-2

Frequencies

GnomAD3 genomes

AF:

0.00483

AC:

735

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00123

AC:

294

AN:

239584

Hom.:

AF XY:

0.000984

AC XY:

129

AN XY:

131164

show subpopulations

Gnomad AFR exome

AF:

0.0175

Gnomad AMR exome

AF:

0.00120

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:

0.0000562

Gnomad OTH exome

AF:

0.000174

GnomAD4 exome

AF:

0.000487

AC:

711

AN:

1459432

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

312

AN XY:

725848

show subpopulations

Gnomad4 AFR exome

AF:

0.0165

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.000980

GnomAD4 genome

AF:

0.00482

AC:

734

AN:

152294

Hom.:

Cov.:

AF XY:

0.00485

AC XY:

361

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0163

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00204

Hom.:

Bravo

AF:

0.00581

ESP6500AA

AF:

0.0110

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00139

AC:

168

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

SRGAP3-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 01, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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

0.080

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.67

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

T;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.0049

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

D;D

MetaRNN

Benign

0.0052

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.98

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.62

N;N

REVEL

Benign

0.070

Sift

Benign

0.42

T;T

Sift4G

Benign

0.31

T;T

Polyphen

0.0

B;B

Vest4

0.36

MVP

0.043

MPC

0.52

ClinPred

0.015

GERP RS

5.1

Varity_R

0.22

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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