rs537658440

Variant names:

• chr15-83576652-C-G
• rs537658440
• NM_003027.5:c.535C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-83576652-C-G
• chr15-83576652-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003027.5(SH3GL3):​c.535C>G​(p.Pro179Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. P179S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SH3GL3 NM_003027.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.42
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21199495).

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.535C>G	p.Pro179Ala	missense	Exon 6 of 9	NP_003018.3
	SH3GL3	NM_001324182.2		c.535C>G	p.Pro179Ala	missense	Exon 6 of 10	NP_001311111.1
	SH3GL3	NM_001301109.2		c.559C>G	p.Pro187Ala	missense	Exon 9 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.535C>G	p.Pro179Ala	missense	Exon 6 of 9	ENSP00000391372.2	Q99963-1
	SH3GL3	ENST00000563901.5	TSL:1	n.*330C>G		non_coding_transcript_exon	Exon 6 of 9	ENSP00000456249.1	H3BRH8
	SH3GL3	ENST00000563901.5	TSL:1	n.*330C>G		3_prime_UTR	Exon 6 of 9	ENSP00000456249.1	H3BRH8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251046 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 6.84e-7 AC: 1 AN: 1461190 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726938

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111466

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.098
Eigen_PC	Benign	0.074
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.9	M
PhyloP100		4.4
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.14
Sift	Benign	0.13	T
Sift4G	Benign	0.081	T
Polyphen		0.0010	B
Vest4		0.32
MutPred		0.50		Gain of MoRF binding (P = 0.0353)
MVP		0.71
MPC		0.89
ClinPred		0.92	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.11

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: rs537658440; hg19: chr15-84245404;