rs1162394

Variant names:

• chr3-9084060-G-C
• rs1162394
• NM_014850.4:c.424-3973C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014850.4(SRGAP3):​c.424-3973C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,006 control chromosomes in the GnomAD database, including 10,466 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 0.36 (10466 hom., cov: 32)
• Consequence: SRGAP3 NM_014850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.411
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRGAP3	NM_014850.4	c.424-3973C>G		intron_variant	Intron 3 of 21	ENST00000383836.8	NP_055665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRGAP3	ENST00000383836.8	c.424-3973C>G		intron_variant	Intron 3 of 21	1	NM_014850.4	ENSP00000373347.3
SRGAP3	ENST00000360413.7	c.424-3973C>G		intron_variant	Intron 3 of 21	1		ENSP00000353587.3
SRGAP3	ENST00000433332.7	n.493-3973C>G		intron_variant	Intron 3 of 17	5
SRGAP3	ENST00000470951.5	n.464-3973C>G		intron_variant	Intron 3 of 5	2

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53996 AN: 151888 Hom.: 10461 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.355 AC: 54033 AN: 152006 Hom.: 10466 Cov.: 32 AF XY: 0.354 AC XY: 26289 AN XY: 74304

African (AFR) AF: 0.208 AC: 8632 AN: 41460

American (AMR) AF: 0.315 AC: 4810 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1428 AN: 3472

East Asian (EAS) AF: 0.349 AC: 1801 AN: 5162

South Asian (SAS) AF: 0.395 AC: 1899 AN: 4808

European-Finnish (FIN) AF: 0.371 AC: 3914 AN: 10554

Middle Eastern (MID) AF: 0.370 AC: 108 AN: 292

European-Non Finnish (NFE) AF: 0.448 AC: 30422 AN: 67960

Other (OTH) AF: 0.363 AC: 766 AN: 2110

Alfa AF: 0.396 Hom.: 1554

Bravo AF: 0.345

Asia WGS AF: 0.353 AC: 1230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.57
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1162394; hg19: chr3-9125744;