Variant chr12-63984040-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_020762.4(SRGAP1):c.161G>A(p.Arg54Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000448 in 1,562,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

SRGAP1
NM_020762.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 9.92

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:

SRGAP1 (HGNC:):

SRGAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.796

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRGAP1	NM_020762.4 linkuse as main transcript	c.161G>A	p.Arg54Gln	missense_variant	2/22	ENST00000355086.8	NP_065813.1	Q7Z6B7-1
SRGAP1	NM_001346201.2 linkuse as main transcript	c.161G>A	p.Arg54Gln	missense_variant	2/22		NP_001333130.1	Q7Z6B7-2
SRGAP1	XM_024449096.2 linkuse as main transcript	c.161G>A	p.Arg54Gln	missense_variant	2/14		XP_024304864.1
SRGAP1	XM_024449097.2 linkuse as main transcript	c.161G>A	p.Arg54Gln	missense_variant	2/12		XP_024304865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRGAP1	ENST00000355086.8 linkuse as main transcript	c.161G>A	p.Arg54Gln	missense_variant	2/22	1	NM_020762.4	ENSP00000347198.3		Q7Z6B7-1

Frequencies

GnomAD3 genomes

AF:

0.00000662

AC:

AN:

151046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000427

AC:

AN:

233944

Hom.:

AF XY:

0.00000787

AC XY:

AN XY:

127142

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000929

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000425

AC:

AN:

1411950

Hom.:

Cov.:

AF XY:

0.00000569

AC XY:

AN XY:

702520

show subpopulations

Gnomad4 AFR exome

AF:

0.0000312

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000462

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000662

AC:

AN:

151046

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73664

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000148

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SRGAP1-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 23, 2023

The SRGAP1 c.161G>A variant is predicted to result in the amino acid substitution p.Arg54Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00093% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-64377820-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

T;T;T

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

1.0

D;D;.

M_CAP

Benign

0.052

MetaRNN

Pathogenic

0.80

D;D;D

MetaSVM

Benign

-0.42

MutationAssessor

Uncertain

2.8

M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.5

D;.;D

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

D;.;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.83

MutPred

0.65

Gain of ubiquitination at K56 (P = 0.0443);.;.;

MVP

0.76

MPC

2.1

ClinPred

1.0

GERP RS

5.3

Varity_R

0.55

gMVP

0.63

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