dbSNP rs180889318: GYPB:p.Ser21Gly (chr4-144001260-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_002100.6(GYPB):c.61A>G(p.Ser21Gly) 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. 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. S21R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GYPB
NM_002100.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.950

Variant links:

Genes affected

GYPB (HGNC:4703): (glycophorin B (MNS blood group)) Glycophorins A (GYPA) and B (GYPB) are major sialoglycoproteins of the human erythrocyte membrane which bear the antigenic determinants for the MN and Ss blood groups. GYPB gene consists of 5 exons and has 97% sequence homology with GYPA from the 5' UTR to the coding sequence encoding the first 45 amino acids. In addition to the M or N and S or s antigens, that commonly occur in all populations, about 40 related variant phenotypes have been identified. These variants include all the variants of the Miltenberger complex and several isoforms of Sta; also, Dantu, Sat, He, Mg, and deletion variants Ena, S-s-U- and Mk. Most of the variants are the result of gene recombinations between GYPA and GYPB. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

GYPB links:

ENSG00000251600 (HGNC:):

ENSG00000251600 links:

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ACMG classification

Classification made for transcript

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
GYPB	NM_002100.6 link	c.61A>G	p.Ser21Gly	missense_variant	Exon 2 of 5	ENST00000502664.6	NP_002091.4	P06028-1
GYPB	XM_011531903.3 link	c.61A>G	p.Ser21Gly	missense_variant	Exon 2 of 5		XP_011530205.1
GYPB	XM_011531904.4 link	c.34A>G	p.Ser12Gly	missense_variant	Exon 3 of 6		XP_011530206.1
GYPB	NM_001304382.1 link	c.-18A>G		5_prime_UTR_variant	Exon 3 of 6		NP_001291311.1	P06028

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GYPB	ENST00000502664.6 link	c.61A>G	p.Ser21Gly	missense_variant	Exon 2 of 5	1	NM_002100.6	ENSP00000427690.1	P06028-1
GYPB	ENST00000504951.6 link	n.*47A>G		non_coding_transcript_exon_variant	Exon 3 of 7	1		ENSP00000421974.2	D6RA87
GYPB	ENST00000504951.6 link	n.*47A>G		3_prime_UTR_variant	Exon 3 of 7	1		ENSP00000421974.2	D6RA87

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1461302

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726964

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.55

DANN

Benign

0.95

DEOGEN2

Benign

0.014

.;T;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0031

LIST_S2

Uncertain

0.86

D;T;D

M_CAP

Benign

0.0011

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-1.1

PROVEAN

Uncertain

-3.8

D;N;.

REVEL

Benign

0.029

Sift

Uncertain

0.010

D;D;.

Sift4G

Pathogenic

0.0

D;T;.

Vest4

0.14

MutPred

0.34

Loss of stability (P = 0.0149);Loss of stability (P = 0.0149);Loss of stability (P = 0.0149);

MVP

0.040

MPC

0.019

ClinPred

0.32

GERP RS

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.089

gMVP

0.023

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.28

Position offset: 23

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over