Variant chr1-25284657-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016124.6(RHD):c.233C>T(p.Ala78Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000074 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RHD
NM_016124.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHD	NM_016124.6 link	c.233C>T	p.Ala78Val	missense_variant	2/10	ENST00000328664.9	NP_057208.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHD	ENST00000328664.9 link	c.233C>T	p.Ala78Val	missense_variant	2/10	1	NM_016124.6	ENSP00000331871.4		Q02161-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

134530

Hom.:

Cov.:

FAILED QC

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:

0.0000176

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000159

AC:

AN:

1254254

Hom.:

Cov.:

AF XY:

0.0000160

AC XY:

AN XY:

625638

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:

0.00

Gnomad4 NFE exome

AF:

0.0000215

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000743

AC:

AN:

134530

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

65984

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:

0.0000176

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 05, 2024

The c.233C>T (p.A78V) alteration is located in exon 2 (coding exon 2) of the RHD gene. This alteration results from a C to T substitution at nucleotide position 233, causing the alanine (A) at amino acid position 78 to be replaced by a valine (V). 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

0.29

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

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

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.58

LIST_S2

Uncertain

0.96

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

M_CAP

Benign

0.0093

MetaRNN

Uncertain

0.64

D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.2

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

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.3

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

REVEL

Benign

0.29

Sift

Uncertain

0.0020

D;.;.;D;D;D;D;D;T

Sift4G

Uncertain

0.0040

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

Polyphen

1.0

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

Vest4

0.59

MutPred

0.71

Loss of disorder (P = 0.1261);Loss of disorder (P = 0.1261);Loss of disorder (P = 0.1261);Loss of disorder (P = 0.1261);Loss of disorder (P = 0.1261);Loss of disorder (P = 0.1261);Loss of disorder (P = 0.1261);Loss of disorder (P = 0.1261);Loss of disorder (P = 0.1261);

MVP

0.16

MPC

0.47

ClinPred

0.96

GERP RS

2.9

Varity_R

0.48

gMVP

0.70

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over