rs1643347472

Variant names:

• chr1-25301028-C-G
• NM_016124.6:c.569C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-25301028-C-G
• chr1-25301028-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016124.6(RHD):​c.569C>G​(p.Pro190Arg) 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 1,246,834 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. P190L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: RHD NM_016124.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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=0.1703046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHD	NM_016124.6	c.569C>G	p.Pro190Arg	missense_variant	Exon 4 of 10	ENST00000328664.9	NP_057208.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHD	ENST00000328664.9	c.569C>G	p.Pro190Arg	missense_variant	Exon 4 of 10	1	NM_016124.6	ENSP00000331871.4

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 8.02e-7 AC: 1 AN: 1246834 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 621850

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: 0.00000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T;.;.;.;.;.;.;.;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.81	T;T;T;T;T;T;T;T;.
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.17	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;.;.;M;M;M;.;M;.
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-4.2	D;.;.;D;D;D;D;D;D
REVEL	Benign	0.061
Sift	Uncertain	0.0030	D;.;.;T;D;D;D;D;D
Sift4G	Benign	0.077	T;.;T;T;T;T;T;T;T
Polyphen		1.0	D;.;P;.;.;.;.;.;P
Vest4		0.23
MutPred		0.43		Loss of catalytic residue at P190 (P = 0.0382);Loss of catalytic residue at P190 (P = 0.0382);Loss of catalytic residue at P190 (P = 0.0382);Loss of catalytic residue at P190 (P = 0.0382);Loss of catalytic residue at P190 (P = 0.0382);Loss of catalytic residue at P190 (P = 0.0382);Loss of catalytic residue at P190 (P = 0.0382);Loss of catalytic residue at P190 (P = 0.0382);Loss of catalytic residue at P190 (P = 0.0382);
MVP		0.27
MPC		0.46
ClinPred		0.90	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.18
gMVP		0.24

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: chr1-25627519;