1-25301070-T-A

Variant names:

• chr1-25301070-T-A
• NM_016124.6:c.611T>A

Variant summary

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

The NM_016124.6(RHD):​c.611T>A​(p.Ile204Lys) 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. Variant has been reported in ClinVar as Affects (no stars).

• Frequency: Genomes: not found (cov: 21)
• Consequence: RHD NM_016124.6 missense
• Clinical Significance: Affects no assertion criteria provided O:1
• Conservation: PhyloP100: 0.0250

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=0.085042566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHD	NM_016124.6	c.611T>A	p.Ile204Lys	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.611T>A	p.Ile204Lys	missense_variant	Exon 4 of 10	1	NM_016124.6	ENSP00000331871.4

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

serologic weak D phenotype Other:1

Sep 04, 2020

Laboratory Services Section, National Institutes of Health

Significance: Affects

Review Status: no assertion criteria provided

Collection Method: clinical testing

The potential of anti-D immunization for the novel NG_007494.1(RHD):c.611T>A allele is unknown. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.47
DANN	Benign	0.79
DEOGEN2	Benign	0.0017	T;.;.;.;.;.;.;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0088	N
LIST_S2	Uncertain	0.88	D;D;D;D;D;D;D;D;.
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.085	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.14	N;.;.;N;N;N;.;N;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	1.0	N;.;.;N;N;N;N;N;N
REVEL	Benign	0.019
Sift	Benign	0.35	T;.;.;T;T;T;T;T;T
Sift4G	Benign	1.0	T;.;T;T;T;T;T;T;T
Polyphen		0.0080	B;.;B;.;.;.;.;.;B
Vest4		0.19
MutPred		0.62		Gain of disorder (P = 0.0019);Gain of disorder (P = 0.0019);Gain of disorder (P = 0.0019);Gain of disorder (P = 0.0019);Gain of disorder (P = 0.0019);Gain of disorder (P = 0.0019);Gain of disorder (P = 0.0019);Gain of disorder (P = 0.0019);Gain of disorder (P = 0.0019);
MVP		0.014
MPC		0.19
ClinPred		0.17	T
GERP RS		0.29
Varity_R		0.032
gMVP		0.35

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: chr1-25627561;