1-25290646-G-C

Position:

• chr1-25290646-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Affects no assertion criteria provided O:1
• Conservation: PhyloP100: -0.542

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 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/exons	MANE	Protein	UniProt
RHD	NM_016124.6	c.341G>C	p.Arg114Pro	missense_variant	3/10	ENST00000328664.9	NP_057208.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHD	ENST00000328664.9	c.341G>C	p.Arg114Pro	missense_variant	3/10	1	NM_016124.6	ENSP00000331871	P1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 8.02e-7 AC: 1 AN: 1246788 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 621866

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.: 20

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

-

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	T
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	N
LIST_S2	Benign	0.80	T;T;T;T;T;T;T;T;.
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.22	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.1	L;.;.;L;L;L;.;L;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.20	T
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	T
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.

Other links and lift over

hg19: chr1-25617137;