rs1491579

Positions:

• chr15-83509927-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

SH3GL3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SH3GL3	NM_003027.5	c.46-49326T>C		intron_variant		ENST00000427482.7	NP_003018.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3GL3	ENST00000427482.7	c.46-49326T>C		intron_variant		1	NM_003027.5	ENSP00000391372.2
SH3GL3	ENST00000492099.1	n.352-49326T>C		intron_variant		1
SH3GL3	ENST00000563901.5	n.46-49326T>C		intron_variant		1		ENSP00000456249.1
SH3GL3	ENST00000324537.5	c.69+19025T>C		intron_variant		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

Gnomad4 AFR AF: 0.791

Gnomad4 AMR AF: 0.704

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.631

Alfa AF: 0.568 Hom.: 34184

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

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: rs1491579; hg19: chr15-84178679;