rs1896796

Positions:

• chr15-83606228-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.839-11854A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,924 control chromosomes in the GnomAD database, including 16,528 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 0.46 (16528 hom., cov: 31)
• Consequence: SH3GL3 NM_003027.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3GL3	NM_003027.5	c.839-11854A>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.839-11854A>G		intron_variant		1	NM_003027.5	ENSP00000391372	P1
SH3GL3	ENST00000563901.5	c.*634-11854A>G		intron_variant, NMD_transcript_variant		1		ENSP00000456249
SH3GL3	ENST00000324537.5	c.863-11854A>G		intron_variant		2		ENSP00000320092

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69744 AN: 151806 Hom.: 16492 Cov.: 31

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.460 AC: 69838 AN: 151924 Hom.: 16528 Cov.: 31 AF XY: 0.455 AC XY: 33820 AN XY: 74260

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.437

Alfa AF: 0.432 Hom.: 14186

Bravo AF: 0.480

Asia WGS AF: 0.361 AC: 1256 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.76

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: rs1896796; hg19: chr15-84274980;