19-581364-G-T

Variant names:

• chr19-581364-G-T
• rs781492579
• NM_001728.4:c.842G>T

Variant summary

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

The NM_001728.4(BSG):​c.842G>T​(p.Gly281Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BSG NM_001728.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.140
• Publications: 1 publications found

Genes affected

BSG (HGNC:1116): (basigin (Ok blood group)) The protein encoded by this gene, basigin, is a plasma membrane protein that is important in spermatogenesis, embryo implantation, neural network formation, and tumor progression. Basigin is also a member of the immunoglobulin superfamily, ubiquitously expressed in various tissues. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2020]

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=0.15887389).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BSG	NM_001728.4	c.842G>T	p.Gly281Val	missense_variant	Exon 6 of 9	ENST00000333511.9	NP_001719.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BSG	ENST00000333511.9	c.842G>T	p.Gly281Val	missense_variant	Exon 6 of 9	1	NM_001728.4	ENSP00000333769.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248986 AF XY: 0.00

Gnomad AFR exome AF: 0.0000620

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 Cov.: 33

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.494G>T (p.G165V) alteration is located in exon 5 (coding exon 5) of the BSG gene. This alteration results from a G to T substitution at nucleotide position 494, causing the glycine (G) at amino acid position 165 to be replaced by a valine (V). 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	Benign	0.18
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	9.7
DANN	Benign	0.91
DEOGEN2	Benign	0.42	.;.;T;.;.;.;T;.
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.81	T;T;T;T;T;T;T;T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.16	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.6	.;.;L;.;.;.;.;.
PhyloP100		0.14
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.2	.;N;D;.;N;.;.;.
REVEL	Benign	0.28
Sift	Benign	0.17	.;T;D;.;D;.;.;.
Sift4G	Benign	0.17	T;T;D;T;D;D;D;D
Polyphen		0.89, 0.86	.;.;P;.;P;.;.;.
Vest4		0.23
MutPred		0.34		.;.;Loss of sheet (P = 0.0457);.;.;.;.;.;
MVP		0.47
MPC		0.31
ClinPred		0.077	T
GERP RS		-6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.24
gMVP		0.61
Mutation Taster		=95/5	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: rs781492579; hg19: chr19-581364;