12-63984024-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2 BP4_Moderate BP6_Very_Strong BP7

The NM_020762.4(SRGAP1):c.145C>T(p.Leu49=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000598 in 1,577,814 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00062 (1 hom.)
• Consequence: SRGAP1 NM_020762.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.73

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 12-63984024-C-T is Benign according to our data. Variant chr12-63984024-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 725157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.73 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRGAP1	NM_020762.4	c.145C>T	p.Leu49=	synonymous_variant	2/22	ENST00000355086.8
SRGAP1	NM_001346201.2	c.145C>T	p.Leu49=	synonymous_variant	2/22
SRGAP1	XM_024449096.2	c.145C>T	p.Leu49=	synonymous_variant	2/14
SRGAP1	XM_024449097.2	c.145C>T	p.Leu49=	synonymous_variant	2/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRGAP1	ENST00000355086.8	c.145C>T	p.Leu49=	synonymous_variant	2/22	1	NM_020762.4	A1

Frequencies

GnomAD3 genomes AF: 0.000364 AC: 55 AN: 151122 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000195

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000632

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000649

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000513 AC: 124 AN: 241682 Hom.: 1 AF XY: 0.000549 AC XY: 72 AN XY: 131194

Gnomad AFR exome AF: 0.000196

Gnomad AMR exome AF: 0.000186

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00167

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000570

Gnomad OTH exome AF: 0.000519

GnomAD4 exome AF: 0.000623 AC: 889 AN: 1426578 Hom.: 1 Cov.: 30 AF XY: 0.000643 AC XY: 456 AN XY: 709594

Gnomad4 AFR exome AF: 0.0000920

Gnomad4 AMR exome AF: 0.000139

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00166

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000654

Gnomad4 OTH exome AF: 0.000530

GnomAD4 genome AF: 0.000364 AC: 55 AN: 151236 Hom.: 0 Cov.: 28 AF XY: 0.000271 AC XY: 20 AN XY: 73806

Gnomad4 AFR AF: 0.000194

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000632

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000649

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000307 Hom.: 0

Bravo AF: 0.000310

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2022	SRGAP1: BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
Cadd	Benign	11
Dann	Benign	0.76

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

Other links and lift over

dbSNP: rs142409169; hg19: chr12-64377804;