6-49607201-CT-C

Position:

• chr6-49607201-CT-C

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_000324.3(RHAG):​c.1086del​(p.Ala363LeufsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RHAG NM_000324.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.249

Genes affected

RHAG (HGNC:10006): (Rh associated glycoprotein) The protein encoded by this gene is erythrocyte-specific and is thought to be part of a membrane channel that transports ammonium and carbon dioxide across the blood cell membrane. The encoded protein appears to interact with Rh blood group antigens and Rh30 polypeptides. Defects in this gene are a cause of regulator type Rh-null hemolytic anemia (RHN), or Rh-deficiency syndrome.[provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 6-49607201-CT-C is Pathogenic according to our data. Variant chr6-49607201-CT-C is described in ClinVar as [Pathogenic]. Clinvar id is 13058.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHAG	NM_000324.3	c.1086del	p.Ala363LeufsTer15	frameshift_variant	8/10	ENST00000371175.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHAG	ENST00000371175.10	c.1086del	p.Ala363LeufsTer15	frameshift_variant	8/10	1	NM_000324.3	P2
RHAG	ENST00000646272.1	c.1086del	p.Ala363LeufsTer15	frameshift_variant	8/10			A2
RHAG	ENST00000646963.1	c.1086del	p.Ala363LeufsTer15	frameshift_variant	8/9
RHAG	ENST00000646939.1	c.964del	p.Ser322AlafsTer48	frameshift_variant	7/9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Rh-null, regulator type Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 01, 1996

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1562011389; hg19: chr6-49574914;