Genetic Variant RHD:p.Arg114Pro (chr1-25290646-G-C) – 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.341G>C(p.Arg114Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000802 in 1,246,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Affects (no stars).

Frequency

Genomes: not found (cov: 20)

Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

RHD
NM_016124.6 missense

Scores

Clinical Significance

Affects no assertion criteria provided O:1

Conservation

PhyloP100: -0.542

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:

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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=0.21755067).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHD	NM_016124.6 link	c.341G>C	p.Arg114Pro	missense_variant	Exon 3 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.341G>C	p.Arg114Pro	missense_variant	Exon 3 of 10	1	NM_016124.6	ENSP00000331871.4		Q02161-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.02e-7

AC:

AN:

1246788

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

621866

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:

0.00

Gnomad4 FIN exome

AF:

0.0000213

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

weakened D expression by serology

Other:1

Australian Red Cross Blood Service

Significance: Affects

Review Status: no assertion criteria provided

Collection Method: research

The c.341G>C variant found on the RHD gene in maternal and infant sample. both show weakened D expression. The change is at the same position as a known allele (RHD*01W.25) however it is not the same base change. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

2.3

DANN

Benign

0.95

DEOGEN2

Benign

0.0032

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

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.80

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

M_CAP

Benign

0.0037

MetaRNN

Benign

0.22

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

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.1

L;.;.;L;L;L;.;L;.

PrimateAI

Benign

0.20

PROVEAN

Benign

-1.6

N;.;.;N;N;N;N;N;N

REVEL

Benign

0.065

Sift

Benign

0.23

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

Sift4G

Benign

0.29

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

Polyphen

0.0090

B;.;B;.;.;.;.;.;B

Vest4

0.27

MutPred

0.72

Loss of catalytic residue at R114 (P = 0.0382);Loss of catalytic residue at R114 (P = 0.0382);Loss of catalytic residue at R114 (P = 0.0382);Loss of catalytic residue at R114 (P = 0.0382);Loss of catalytic residue at R114 (P = 0.0382);Loss of catalytic residue at R114 (P = 0.0382);Loss of catalytic residue at R114 (P = 0.0382);Loss of catalytic residue at R114 (P = 0.0382);Loss of catalytic residue at R114 (P = 0.0382);

MVP

0.28

MPC

0.14

ClinPred

0.074

GERP RS

-5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.29

gMVP

0.81

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over