NM_000324.3:c.1085C>A

Variant names:

• chr6-49607203-G-T
• rs1327883064
• NM_000324.3:c.1085C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000324.3(RHAG):​c.1085C>A​(p.Ala362Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: RHAG NM_000324.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.44

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHAG	NM_000324.3	c.1085C>A	p.Ala362Glu	missense_variant	Exon 8 of 10	ENST00000371175.10	NP_000315.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHAG	ENST00000371175.10	c.1085C>A	p.Ala362Glu	missense_variant	Exon 8 of 10	1	NM_000324.3	ENSP00000360217.4
RHAG	ENST00000646272.1	c.1085C>A	p.Ala362Glu	missense_variant	Exon 8 of 10			ENSP00000494337.1
RHAG	ENST00000646963.1	c.1085C>A	p.Ala362Glu	missense_variant	Exon 8 of 9			ENSP00000495337.1
RHAG	ENST00000646939.1	c.963C>A	p.Gly321Gly	synonymous_variant	Exon 7 of 9			ENSP00000494709.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461228 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726886

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.;T;T;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.89	D;D;D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.80	D;D;D;D;D
MetaSVM	Benign	-0.73	T
MutationAssessor	Pathogenic	3.5	H;.;.;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.1	D;.;.;.;.
REVEL	Uncertain	0.34
Sift	Benign	0.17	T;.;.;.;.
Sift4G	Benign	0.22	T;.;T;T;.
Polyphen		0.96	P;.;.;.;D
Vest4		0.76
MutPred		0.76		Gain of disorder (P = 0.0449);Gain of disorder (P = 0.0449);Gain of disorder (P = 0.0449);Gain of disorder (P = 0.0449);Gain of disorder (P = 0.0449);
MVP		0.40
MPC		1.0
ClinPred		0.94	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.39
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1327883064; hg19: chr6-49574916;