rs35647176

Positions:

• chr3-9037444-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000383836.8(SRGAP3):​c.1436+619C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 154,226 control chromosomes in the GnomAD database, including 2,310 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 0.17 (2282 hom., cov: 33)
  • Exomes 𝑓: 0.15 (28 hom.)
• Consequence: SRGAP3 ENST00000383836.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.558

Genes affected

SRGAP3 (HGNC:19744): (SLIT-ROBO Rho GTPase activating protein 3) Predicted to enable GTPase activator activity. Predicted to be involved in negative regulation of cell migration. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRGAP3	NM_014850.4	c.1436+619C>T		intron_variant		ENST00000383836.8	NP_055665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRGAP3	ENST00000383836.8	c.1436+619C>T		intron_variant		1	NM_014850.4	ENSP00000373347	P1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25251 AN: 152004 Hom.: 2286 Cov.: 33

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0382

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.147 AC: 309 AN: 2104 Hom.: 28 Cov.: 0 AF XY: 0.147 AC XY: 160 AN XY: 1088

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0881

Gnomad4 ASJ exome AF: 0.100

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.183

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.128

GnomAD4 genome AF: 0.166 AC: 25241 AN: 152122 Hom.: 2282 Cov.: 33 AF XY: 0.164 AC XY: 12223 AN XY: 74368

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.0380

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.176

Alfa AF: 0.193 Hom.: 627

Bravo AF: 0.156

Asia WGS AF: 0.103 AC: 360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	14
DANN	Benign	0.80

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: rs35647176; hg19: chr3-9079128;