1-26281072-C-G

Variant names:

• chr1-26281072-C-G
• NM_031286.4:c.231C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031286.4(SH3BGRL3):​c.231C>G​(p.Phe77Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SH3BGRL3 NM_031286.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.188

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3BGRL3	NM_031286.4	c.231C>G	p.Phe77Leu	missense_variant	Exon 3 of 3	ENST00000270792.10	NP_112576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3BGRL3	ENST00000270792.10	c.231C>G	p.Phe77Leu	missense_variant	Exon 3 of 3	1	NM_031286.4	ENSP00000270792.5
SH3BGRL3	ENST00000319041.6	c.*89C>G		3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000363358.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.231C>G (p.F77L) alteration is located in exon 3 (coding exon 3) of the SH3BGRL3 gene. This alteration results from a C to G substitution at nucleotide position 231, causing the phenylalanine (F) at amino acid position 77 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Benign	0.069
Eigen_PC	Benign	0.088
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.85	T
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.49	T
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.48
Sift	Benign	0.052	T
Sift4G	Benign	0.062	T
Polyphen		0.66	P
Vest4		0.30
MutPred		0.83		Loss of catalytic residue at F77 (P = 0.0357);
MVP		0.40
MPC		0.55
ClinPred		0.95	D
GERP RS		3.5
Varity_R		0.59
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-26607563;