15-83568582-G-A

Variant names:

• chr15-83568582-G-A
• rs764980950
• NM_003027.5:c.241G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_003027.5(SH3GL3):​c.241G>A​(p.Val81Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V81L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: SH3GL3 NM_003027.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.39
• Publications: 2 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3339357).
• BS2: High AC in GnomAdExome4 at 14 AD gene.

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.241G>A	p.Val81Met	missense	Exon 4 of 9	NP_003018.3
	SH3GL3	NM_001324182.2		c.241G>A	p.Val81Met	missense	Exon 4 of 10	NP_001311111.1
	SH3GL3	NM_001301109.2		c.265G>A	p.Val89Met	missense	Exon 7 of 12	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.241G>A	p.Val81Met	missense	Exon 4 of 9	ENSP00000391372.2	Q99963-1
	SH3GL3	ENST00000563901.5	TSL:1	n.*36G>A		non_coding_transcript_exon	Exon 4 of 9	ENSP00000456249.1	H3BRH8
	SH3GL3	ENST00000563901.5	TSL:1	n.*36G>A		3_prime_UTR	Exon 4 of 9	ENSP00000456249.1	H3BRH8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000438 AC: 11 AN: 251286 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461198 Hom.: 0 Cov.: 29 AF XY: 0.00000550 AC XY: 4 AN XY: 726992

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.000268 AC: 12 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111404

Other (OTH) AF: 0.00 AC: 0 AN: 60360

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.4
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.12
Sift	Benign	0.062	T
Sift4G	Benign	0.098	T
Polyphen		0.62	P
Vest4		0.56
MutPred		0.49		Loss of methylation at K82 (P = 0.0158)
MVP		0.53
MPC		1.1
ClinPred		0.39	T
GERP RS		3.9
Varity_R		0.19
gMVP		0.35
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs764980950; hg19: chr15-84237334;