rs1491579

Variant names:

• chr15-83509927-T-C
• rs1491579
• NM_003027.5:c.46-49326T>C

Variant summary

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

The NM_003027.5(SH3GL3):​c.46-49326T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 151,942 control chromosomes in the GnomAD database, including 29,736 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 0.61 (29736 hom., cov: 31)
• Consequence: SH3GL3 NM_003027.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245
• Publications: 7 publications found

Genes affected

SH3GL3 (HGNC:10832): (SH3 domain containing GRB2 like 3, endophilin A3) Enables identical protein binding activity. Predicted to be involved in synaptic vesicle uncoating. Predicted to be located in acrosomal vesicle; early endosome membrane; and presynapse. Predicted to be part of early endosome. Predicted to be active in glutamatergic synapse; postsynaptic density, intracellular component; and postsynaptic endosome. [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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3GL3	NM_003027.5	c.46-49326T>C		intron_variant	Intron 1 of 8	ENST00000427482.7	NP_003018.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3GL3	ENST00000427482.7	c.46-49326T>C		intron_variant	Intron 1 of 8	1	NM_003027.5	ENSP00000391372.2
SH3GL3	ENST00000492099.1	n.352-49326T>C		intron_variant	Intron 1 of 2	1
SH3GL3	ENST00000563901.5	n.46-49326T>C		intron_variant	Intron 1 of 8	1		ENSP00000456249.1
SH3GL3	ENST00000324537.5	c.69+19025T>C		intron_variant	Intron 4 of 11	2		ENSP00000320092.5

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92749 AN: 151824 Hom.: 29705 Cov.: 31

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.611 AC: 92830 AN: 151942 Hom.: 29736 Cov.: 31 AF XY: 0.601 AC XY: 44662 AN XY: 74262

African (AFR) AF: 0.791 AC: 32815 AN: 41460

American (AMR) AF: 0.704 AC: 10743 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2270 AN: 3472

East Asian (EAS) AF: 0.506 AC: 2603 AN: 5140

South Asian (SAS) AF: 0.337 AC: 1618 AN: 4806

European-Finnish (FIN) AF: 0.396 AC: 4182 AN: 10552

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36619 AN: 67936

Other (OTH) AF: 0.631 AC: 1327 AN: 2104

Alfa AF: 0.578 Hom.: 44540

Bravo AF: 0.648

Asia WGS AF: 0.451 AC: 1567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.40
PhyloP100		-0.24
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: rs1491579; hg19: chr15-84178679;