1-25301038-G-T

Variant names:

• chr1-25301038-G-T
• rs77813628
• NM_016124.6:c.579G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016124.6(RHD):​c.579G>T​(p.Glu193Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. E193K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 21)
• Consequence: RHD NM_016124.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.833

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051997334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHD	NM_016124.6	c.579G>T	p.Glu193Asp	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.579G>T	p.Glu193Asp	missense_variant	Exon 4 of 10	1	NM_016124.6	ENSP00000331871.4

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD3 exomes AF: 0.00000445 AC: 1 AN: 224764 Hom.: 0 AF XY: 0.00000826 AC XY: 1 AN XY: 121096

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 21

ExAC AF: 0.00000894 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.18
DANN	Benign	0.58
DEOGEN2	Benign	0.0040	T;.;.;.;.;.;.;.;.
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0056	N
LIST_S2	Benign	0.28	T;T;T;T;T;T;T;T;.
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.052	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.52	N;.;.;N;N;N;.;N;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.1	N;.;.;N;N;N;N;N;N
REVEL	Benign	0.0080
Sift	Benign	0.074	T;.;.;T;T;T;T;T;T
Sift4G	Benign	0.34	T;.;T;T;T;T;T;T;T
Polyphen		0.0	B;.;B;.;.;.;.;.;B
Vest4		0.15
MutPred		0.28		Loss of catalytic residue at E193 (P = 0.0771);Loss of catalytic residue at E193 (P = 0.0771);Loss of catalytic residue at E193 (P = 0.0771);Loss of catalytic residue at E193 (P = 0.0771);Loss of catalytic residue at E193 (P = 0.0771);Loss of catalytic residue at E193 (P = 0.0771);Loss of catalytic residue at E193 (P = 0.0771);Loss of catalytic residue at E193 (P = 0.0771);Loss of catalytic residue at E193 (P = 0.0771);
MVP		0.076
MPC		0.078
ClinPred		0.085	T
GERP RS		-7.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.048
gMVP		0.16

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

Other links and lift over

dbSNP: rs77813628; hg19: chr1-25627529;