rs1248638537

Variant names:

• chr1-25284694-G-A
• rs1248638537
• NM_016124.6:c.270G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-25284694-G-A
• chr1-25284694-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016124.6(RHD):​c.270G>A​(p.Trp90*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RHD NM_016124.6 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016124.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHD	NM_016124.6	MANE Select	c.270G>A	p.Trp90*	stop_gained	Exon 2 of 10	NP_057208.3
	RHD	NM_001282871.2		c.270G>A	p.Trp90*	stop_gained	Exon 2 of 9	NP_001269800.1	Q02161-4
	RHD	NM_001282870.1		c.270G>A	p.Trp90*	stop_gained	Exon 2 of 9	NP_001269799.1	Q5XLT0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHD	ENST00000328664.9	TSL:1 MANE Select	c.270G>A	p.Trp90*	stop_gained	Exon 2 of 10	ENSP00000331871.4	Q02161-1
	RHD	ENST00000342055.9	TSL:1	c.270G>A	p.Trp90*	stop_gained	Exon 2 of 9	ENSP00000339577.5	Q02161-4
	RHD	ENST00000568195.5	TSL:1	c.270G>A	p.Trp90*	stop_gained	Exon 2 of 9	ENSP00000456966.1	H3BT10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.44
CADD	Pathogenic	34
DANN	Uncertain	0.99
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.046
FATHMM_MKL	Benign	0.69	D
PhyloP100		1.7
Vest4		0.89
GERP RS		1.9
Mutation Taster		=23/177	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs1248638537; hg19: chr1-25611185;