19-580441-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001728.4(BSG):​c.635C>T​(p.Thr212Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000807 in 1,610,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

BSG
NM_001728.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.159
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15448776).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BSGNM_001728.4 linkc.635C>T p.Thr212Met missense_variant Exon 4 of 9 ENST00000333511.9 NP_001719.2 P35613-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BSGENST00000333511.9 linkc.635C>T p.Thr212Met missense_variant Exon 4 of 9 1 NM_001728.4 ENSP00000333769.3 P35613-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152088
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000807
AC:
2
AN:
247958
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
134770
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000178
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000823
AC:
12
AN:
1458676
Hom.:
0
Cov.:
34
AF XY:
0.0000110
AC XY:
8
AN XY:
725732
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000719
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152088
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000302
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.00000825
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 15, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.287C>T (p.T96M) alteration is located in exon 3 (coding exon 3) of the BSG gene. This alteration results from a C to T substitution at nucleotide position 287, causing the threonine (T) at amino acid position 96 to be replaced by a methionine (M). 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
0.071
BayesDel_addAF
Benign
-0.039
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
15
DANN
Benign
0.93
DEOGEN2
Benign
0.39
.;.;T;.;.;.;.;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.061
N
LIST_S2
Benign
0.53
T;T;T;T;T;T;T;T
M_CAP
Uncertain
0.19
D
MetaRNN
Benign
0.15
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.0
.;.;N;.;.;.;.;.
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.89
.;N;N;.;N;.;.;.
REVEL
Benign
0.084
Sift
Benign
0.036
.;D;D;.;D;.;.;.
Sift4G
Uncertain
0.051
T;T;T;D;T;D;D;D
Polyphen
0.89, 0.68
.;.;P;.;P;.;.;.
Vest4
0.098
MutPred
0.38
.;.;Loss of glycosylation at T212 (P = 0.0341);.;.;.;.;.;
MVP
0.92
MPC
0.47
ClinPred
0.20
T
GERP RS
-3.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.038
gMVP
0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs567629506; hg19: chr19-580441; API