dbSNP rs139501061: RHD:p.Ala85Gly (chr1-25284678-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_016124.6(RHD):c.254C>G(p.Ala85Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000319 in 1,254,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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. A85V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000032 ( 0 hom. )

Consequence

RHD
NM_016124.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.369

Variant links:

Genes affected

RHD (HGNC:10009): (Rh blood group D antigen) The Rh blood group system is the second most clinically significant of the blood groups, second only to ABO. It is also the most polymorphic of the blood groups, with variations due to deletions, gene conversions, and missense mutations. The Rh blood group includes this gene, which encodes the RhD protein, and a second gene that encodes both the RhC and RhE antigens on a single polypeptide. The two genes, and a third unrelated gene, are found in a cluster on chromosome 1. The classification of Rh-positive and Rh-negative individuals is determined by the presence or absence of the highly immunogenic RhD protein on the surface of erythrocytes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RHD links:

RSRP1 (HGNC:25234): (arginine and serine rich protein 1)

RSRP1 links:

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=0.23002982).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHD	NM_016124.6 link	c.254C>G	p.Ala85Gly	missense_variant	Exon 2 of 10	ENST00000328664.9	NP_057208.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHD	ENST00000328664.9 link	c.254C>G	p.Ala85Gly	missense_variant	Exon 2 of 10	1	NM_016124.6	ENSP00000331871.4		Q02161-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000443

AC:

AN:

225700

Hom.:

AF XY:

0.00000822

AC XY:

AN XY:

121598

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:

0.0000104

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000319

AC:

AN:

1254336

Hom.:

Cov.:

AF XY:

0.00000160

AC XY:

AN XY:

625646

show subpopulations

Gnomad4 AFR exome

AF:

0.0000618

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:

0.00000215

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000180

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.039

T;.;.;.;.;.;.;.;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.67

T;T;T;T;T;T;T;T;.

M_CAP

Benign

0.0061

MetaRNN

Benign

0.23

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Pathogenic

3.1

M;.;.;M;M;M;.;M;.

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.4

D;.;.;D;D;D;D;D;D

REVEL

Benign

0.12

Sift

Uncertain

0.010

D;.;.;D;D;D;D;D;D

Sift4G

Pathogenic

0.0010

D;.;D;D;D;D;D;D;D

Polyphen

0.25

B;.;D;.;.;.;.;.;D

Vest4

0.36

MVP

0.25

MPC

0.099

ClinPred

0.64

GERP RS

2.0

Varity_R

0.24

gMVP

0.45

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.

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