chr1-26280162-G-C

Variant names:

• chr1-26280162-G-C
• rs950277669
• NM_031286.4:c.7G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031286.4(SH3BGRL3):​c.7G>C​(p.Gly3Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,412,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. G3C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SH3BGRL3 NM_031286.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• Publications: 0 publications found

Genes affected

SH3BGRL3 (HGNC:15568): (SH3 domain binding glutamate rich protein like 3) Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2693392).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031286.4. 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
	SH3BGRL3	NM_031286.4	MANE Select	c.7G>C	p.Gly3Arg	missense	Exon 1 of 3	NP_112576.1	Q9H299

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BGRL3	ENST00000270792.10	TSL:1 MANE Select	c.7G>C	p.Gly3Arg	missense	Exon 1 of 3	ENSP00000270792.5	Q9H299
	SH3BGRL3	ENST00000879854.1		c.7G>C	p.Gly3Arg	missense	Exon 1 of 3	ENSP00000549913.1
	SH3BGRL3	ENST00000934912.1		c.7G>C	p.Gly3Arg	missense	Exon 1 of 3	ENSP00000604971.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1412870 Hom.: 0 Cov.: 31 AF XY: 0.00000286 AC XY: 2 AN XY: 699706

African (AFR) AF: 0.00 AC: 0 AN: 31226

American (AMR) AF: 0.00 AC: 0 AN: 37270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24892

East Asian (EAS) AF: 0.00 AC: 0 AN: 36584

South Asian (SAS) AF: 0.00 AC: 0 AN: 80800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5402

European-Non Finnish (NFE) AF: 0.00000184 AC: 2 AN: 1089518

Other (OTH) AF: 0.00 AC: 0 AN: 58374

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.0022	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.67	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.72	T
PhyloP100		1.8
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.21
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.046	D
Polyphen		0.27	B
Vest4		0.25
MutPred		0.46		Gain of methylation at G3 (P = 0.0071)
MVP		0.53
MPC		0.70
ClinPred		0.99	D
GERP RS		5.1
PromoterAI		-0.23	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.28
gMVP		0.58
Mutation Taster		=76/24	polymorphism

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: rs950277669; hg19: chr1-26606653;