1-25301594-G-A

Position:

• chr1-25301594-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000328664.9(RHD):​c.709G>A​(p.Ala237Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Affects (no stars).

• Frequency: Genomes: not found (cov: 21)
• Consequence: RHD ENST00000328664.9 missense
• Clinical Significance: Affects no assertion criteria provided O:1
• Conservation: PhyloP100: 4.39

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]

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

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.914

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHD	NM_016124.6	c.709G>A	p.Ala237Thr	missense_variant	5/10	ENST00000328664.9	NP_057208.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHD	ENST00000328664.9	c.709G>A	p.Ala237Thr	missense_variant	5/10	1	NM_016124.6	ENSP00000331871	P1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 21

ClinVar

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

weakened D expression by serology Other:1

Affects, no assertion criteria provided

research

Australian Red Cross Blood Service

Jul 01, 2021

We have found this nucleotide change RHDc.709G>A in three different samples. All showing weakened D expression on serology. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.048	T;.;.;.;.;.;.;.;.
Eigen	Benign	0.14
Eigen_PC	Benign	-0.029
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.93	D;D;D;D;D;D;D;D;.
M_CAP	Benign	0.0072	T
MetaRNN	Pathogenic	0.91	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.1	M;.;.;M;M;M;.;M;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-3.2	D;.;.;D;D;D;D;D;D
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D;.;.;T;T;T;T;T;T
Sift4G	Benign	0.11	T;.;T;T;T;T;T;T;T
Polyphen		1.0	D;.;D;.;.;.;.;.;D
Vest4		0.40
MutPred		0.79		Gain of ubiquitination at K235 (P = 0.0972);Gain of ubiquitination at K235 (P = 0.0972);Gain of ubiquitination at K235 (P = 0.0972);Gain of ubiquitination at K235 (P = 0.0972);Gain of ubiquitination at K235 (P = 0.0972);Gain of ubiquitination at K235 (P = 0.0972);Gain of ubiquitination at K235 (P = 0.0972);Gain of ubiquitination at K235 (P = 0.0972);Gain of ubiquitination at K235 (P = 0.0972);
MVP		0.28
MPC		0.46
ClinPred		0.98	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.43
gMVP		0.60

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.

Other links and lift over

hg19: chr1-25628085;