NM_001728.4:c.524G>C

Variant names:

• chr19-579608-G-C
• NM_001728.4:c.524G>C

Variant summary

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

The NM_001728.4(BSG):​c.524G>C​(p.Gly175Ala) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G175V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: BSG NM_001728.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.470

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

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
BSG	NM_001728.4	c.524G>C	p.Gly175Ala	missense_variant	Exon 3 of 9	ENST00000333511.9	NP_001719.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BSG	ENST00000333511.9	c.524G>C	p.Gly175Ala	missense_variant	Exon 3 of 9	1	NM_001728.4	ENSP00000333769.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.176G>C (p.G59A) alteration is located in exon 2 (coding exon 2) of the BSG gene. This alteration results from a G to C substitution at nucleotide position 176, causing the glycine (G) at amino acid position 59 to be replaced by an alanine (A). 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	0.13
BayesDel_addAF	Benign	0.0038	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	8.4
DANN	Benign	0.97
DEOGEN2	Pathogenic	0.80	D;.;.;.
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.74	T;D;T;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.54	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;.;.;.
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-4.3	D;.;D;.
REVEL	Benign	0.12
Sift	Uncertain	0.0030	D;.;D;.
Sift4G	Uncertain	0.029	D;T;T;T
Polyphen		0.80	P;.;P;.
Vest4		0.23
MutPred		0.62		Gain of ubiquitination at K179 (P = 0.1165);.;.;.;
MVP		0.61
MPC		0.31
ClinPred		0.90	D
GERP RS		-7.2
Varity_R		0.35
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-579608;