Variant 12-64126026-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_020762.4(SRGAP1):c.2274T>C(p.Ser758=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,613,758 control chromosomes in the GnomAD database, including 227,546 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 25440 hom., cov: 32)

Exomes 𝑓: 0.52 ( 202106 hom. )

Consequence

SRGAP1
NM_020762.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.51

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP7

Synonymous conserved (PhyloP=-2.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SRGAP1	NM_020762.4 linkuse as main transcript	c.2274T>C	p.Ser758=	synonymous_variant	19/22	ENST00000355086.8	NP_065813.1
LOC105369798	XR_945018.2 linkuse as main transcript	n.559+4148A>G		intron_variant, non_coding_transcript_variant
SRGAP1	NM_001346201.2 linkuse as main transcript	c.2205T>C	p.Ser735=	synonymous_variant	19/22		NP_001333130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRGAP1	ENST00000355086.8 linkuse as main transcript	c.2274T>C	p.Ser758=	synonymous_variant	19/22	1	NM_020762.4	ENSP00000347198	A1	Q7Z6B7-1
SRGAP1	ENST00000543397.1 linkuse as main transcript	n.3560T>C		non_coding_transcript_exon_variant	18/21	1
	ENST00000658485.1 linkuse as main transcript	n.366+4148A>G		intron_variant, non_coding_transcript_variant
SRGAP1	ENST00000631006.3 linkuse as main transcript	c.2205T>C	p.Ser735=	synonymous_variant	19/22	5		ENSP00000485752	P3	Q7Z6B7-2

Frequencies

GnomAD3 genomes

AF:

0.572

AC:

86960

AN:

151946

Hom.:

25410

Cov.:

show subpopulations

Gnomad AFR

AF:

0.691

Gnomad AMI

AF:

0.666

Gnomad AMR

AF:

0.519

Gnomad ASJ

AF:

0.559

Gnomad EAS

AF:

0.655

Gnomad SAS

AF:

0.539

Gnomad FIN

AF:

0.555

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.511

Gnomad OTH

AF:

0.551

GnomAD3 exomes

AF:

0.538

AC:

135164

AN:

251202

Hom.:

37105

AF XY:

0.537

AC XY:

72877

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.696

Gnomad AMR exome

AF:

0.450

Gnomad ASJ exome

AF:

0.563

Gnomad EAS exome

AF:

0.640

Gnomad SAS exome

AF:

0.534

Gnomad FIN exome

AF:

0.557

Gnomad NFE exome

AF:

0.521

Gnomad OTH exome

AF:

0.539

GnomAD4 exome

AF:

0.523

AC:

763931

AN:

1461694

Hom.:

202106

Cov.:

AF XY:

0.523

AC XY:

380292

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.700

Gnomad4 AMR exome

AF:

0.461

Gnomad4 ASJ exome

AF:

0.561

Gnomad4 EAS exome

AF:

0.686

Gnomad4 SAS exome

AF:

0.537

Gnomad4 FIN exome

AF:

0.560

Gnomad4 NFE exome

AF:

0.509

Gnomad4 OTH exome

AF:

0.539

GnomAD4 genome

AF:

0.572

AC:

87040

AN:

152064

Hom.:

25440

Cov.:

AF XY:

0.576

AC XY:

42792

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.691

Gnomad4 AMR

AF:

0.519

Gnomad4 ASJ

AF:

0.559

Gnomad4 EAS

AF:

0.655

Gnomad4 SAS

AF:

0.539

Gnomad4 FIN

AF:

0.555

Gnomad4 NFE

AF:

0.511

Gnomad4 OTH

AF:

0.549

Alfa

AF:

0.527

Hom.:

50852

Bravo

AF:

0.571

Asia WGS

AF:

0.559

AC:

1942

AN:

3478

EpiCase

AF:

0.518

EpiControl

AF:

0.514

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.39

DANN

Benign

0.56

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over