Variant 1-121374113-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_001329984.2(SRGAP2C):c.629C>T(p.Thr210Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00039 ( 7 hom., cov: 12)

Exomes 𝑓: 0.00041 ( 50 hom. )

Failed GnomAD Quality Control

Consequence

SRGAP2C
NM_001329984.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.74

Variant links:

Genes affected

SRGAP2C (HGNC:30584): (SLIT-ROBO Rho GTPase activating protein 2C) This locus encodes a member of the SLIT-ROBO Rho GTPase activating protein family. This human-specific locus resulted from segmental duplication of the SLIT-ROBO Rho GTPase activating protein 2B locus. The encoded protein lacks the GTPase activating protein domain compared to proteins encoded by SLIT-ROBO Rho GTPase activating protein 2, and acts antagonistically to these proteins in cortical neuron development. [provided by RefSeq, Dec 2012]

SRGAP2C links:

SRGAP2-AS1 (HGNC:):

SRGAP2-AS1 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=0.0052003562).

BP6

Variant 1-121374113-C-T is Benign according to our data. Variant chr1-121374113-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2639057.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 50 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRGAP2C	NM_001329984.2 linkuse as main transcript	c.629C>T	p.Thr210Met	missense_variant	6/10	ENST00000367123.8	NP_001316913.1	P0DJJ0
SRGAP2C	NM_001271872.3 linkuse as main transcript	c.629C>T	p.Thr210Met	missense_variant	6/10		NP_001258801.1
SRGAP2-AS1	NR_104189.1 linkuse as main transcript	n.330-11225G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SRGAP2C	ENST00000367123.8 linkuse as main transcript	c.629C>T	p.Thr210Met	missense_variant	6/10	5	NM_001329984.2	ENSP00000478290.1	P0DJJ0
SRGAP2C	ENST00000304465.7 linkuse as main transcript	c.170C>T	p.Thr57Met	missense_variant	3/7	5		ENSP00000483477.1	A0A087X0L1
SRGAP2-AS1	ENST00000437515.1 linkuse as main transcript	n.330-11225G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

83014

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000388

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000477

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00912

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000119

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000369

AC:

AN:

165338

Hom.:

AF XY:

0.000327

AC XY:

AN XY:

88562

show subpopulations

Gnomad AFR exome

AF:

0.000245

Gnomad AMR exome

AF:

0.000314

Gnomad ASJ exome

AF:

0.000116

Gnomad EAS exome

AF:

0.00213

Gnomad SAS exome

AF:

0.0000838

Gnomad FIN exome

AF:

0.0000602

Gnomad NFE exome

AF:

0.000255

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000406

AC:

168

AN:

413634

Hom.:

Cov.:

AF XY:

0.000425

AC XY:

AN XY:

225962

show subpopulations

Gnomad4 AFR exome

AF:

0.000195

Gnomad4 AMR exome

AF:

0.000622

Gnomad4 ASJ exome

AF:

0.0000660

Gnomad4 EAS exome

AF:

0.00228

Gnomad4 SAS exome

AF:

0.000108

Gnomad4 FIN exome

AF:

0.0000661

Gnomad4 NFE exome

AF:

0.000271

Gnomad4 OTH exome

AF:

0.00179

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000385

AC:

AN:

83092

Hom.:

Cov.:

AF XY:

0.000324

AC XY:

AN XY:

40098

show subpopulations

Gnomad4 AFR

AF:

0.000387

Gnomad4 AMR

AF:

0.000477

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00913

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000119

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000384

Hom.:

ExAC

AF:

0.000404

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

SRGAP2C: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Benign

0.87

DEOGEN2

Benign

0.0062

T;.

FATHMM_MKL

Benign

0.042

LIST_S2

Uncertain

0.96

D;D

MetaRNN

Benign

0.0052

T;T

Sift4G

Benign

0.14

T;T

Vest4

0.23

MVP

0.14

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.094

gMVP

0.24

Splicing

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