rs2562784

Positions:

• chr15-83617740-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003027.5(SH3GL3):​c.839-342A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,104 control chromosomes in the GnomAD database, including 6,713 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 0.29 (6713 hom., cov: 33)
• Consequence: SH3GL3 NM_003027.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3GL3	NM_003027.5	c.839-342A>G		intron_variant		ENST00000427482.7	NP_003018.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3GL3	ENST00000427482.7	c.839-342A>G		intron_variant		1	NM_003027.5	ENSP00000391372	P1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44028 AN: 151984 Hom.: 6696 Cov.: 33

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.290 AC: 44092 AN: 152104 Hom.: 6713 Cov.: 33 AF XY: 0.295 AC XY: 21945 AN XY: 74354

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.292

Alfa AF: 0.250 Hom.: 10924

Bravo AF: 0.300

Asia WGS AF: 0.369 AC: 1280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.67
DANN	Benign	0.68

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: rs2562784; hg19: chr15-84286492;