chr12-63871057-G-C

Position:

• chr12-63871057-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000355086.8(SRGAP1):​c.67+26174G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: SRGAP1 ENST00000355086.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRGAP1	NM_020762.4	c.67+26174G>C		intron_variant		ENST00000355086.8	NP_065813.1
SRGAP1	NM_001346201.2	c.67+26174G>C		intron_variant			NP_001333130.1
SRGAP1	XM_024449096.2	c.67+26174G>C		intron_variant			XP_024304864.1
SRGAP1	XM_024449097.2	c.67+26174G>C		intron_variant			XP_024304865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRGAP1	ENST00000355086.8	c.67+26174G>C		intron_variant		1	NM_020762.4	ENSP00000347198	A1
SRGAP1	ENST00000631006.3	c.67+26174G>C		intron_variant		5		ENSP00000485752	P3
SRGAP1	ENST00000695902.1	c.67+26174G>C		intron_variant, NMD_transcript_variant				ENSP00000512252
SRGAP1	ENST00000537556.1	n.81+26174G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.38
DANN	Benign	0.48

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: rs11175194; hg19: chr12-64264837;