chr15-83606228-A-G

Variant names:

• chr15-83606228-A-G
• rs1896796
• NM_003027.5:c.839-11854A>G

Variant summary

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003027.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3GL3	NM_003027.5	MANE Select	c.839-11854A>G		intron	N/A	NP_003018.3
	SH3GL3	NM_001324182.2		c.839-5190A>G		intron	N/A	NP_001311111.1
	SH3GL3	NM_001301109.2		c.863-11854A>G		intron	N/A	NP_001288038.1	Q99963-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3GL3	ENST00000427482.7	TSL:1 MANE Select	c.839-11854A>G		intron	N/A	ENSP00000391372.2	Q99963-1
	SH3GL3	ENST00000563901.5	TSL:1	n.*634-11854A>G		intron	N/A	ENSP00000456249.1	H3BRH8
	SH3GL3	ENST00000903482.1		c.905-11854A>G		intron	N/A	ENSP00000573541.1

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

African (AFR) AF: 0.550 AC: 22758 AN: 41394

American (AMR) AF: 0.573 AC: 8756 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1296 AN: 3466

East Asian (EAS) AF: 0.390 AC: 2010 AN: 5154

South Asian (SAS) AF: 0.281 AC: 1351 AN: 4810

European-Finnish (FIN) AF: 0.358 AC: 3779 AN: 10556

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28327 AN: 67944

Other (OTH) AF: 0.437 AC: 923 AN: 2110

Alfa AF: 0.434 Hom.: 17311

Bravo AF: 0.480

Asia WGS AF: 0.361 AC: 1256 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.76
PhyloP100		-0.076
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: rs1896796; hg19: chr15-84274980;