rs139501061

Variant names:

• chr1-25284678-C-G
• rs139501061
• NM_016124.6:c.254C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-25284678-C-G
• chr1-25284678-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016124.6(RHD):​c.254C>G​(p.Ala85Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000319 in 1,254,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. A85V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: RHD NM_016124.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.369
• Publications: 11 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23002982).

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.254C>G	p.Ala85Gly	missense	Exon 2 of 10	NP_057208.3
	RHD	NM_001282871.2		c.254C>G	p.Ala85Gly	missense	Exon 2 of 9	NP_001269800.1	Q02161-4
	RHD	NM_001282870.1		c.254C>G	p.Ala85Gly	missense	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.254C>G	p.Ala85Gly	missense	Exon 2 of 10	ENSP00000331871.4	Q02161-1
	RHD	ENST00000342055.9	TSL:1	c.254C>G	p.Ala85Gly	missense	Exon 2 of 9	ENSP00000339577.5	Q02161-4
	RHD	ENST00000568195.5	TSL:1	c.254C>G	p.Ala85Gly	missense	Exon 2 of 9	ENSP00000456966.1	H3BT10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000443 AC: 1 AN: 225700 AF XY: 0.00000822

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000104

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000319 AC: 4 AN: 1254336 Hom.: 0 Cov.: 34 AF XY: 0.00000160 AC XY: 1 AN XY: 625646

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000618 AC: 2 AN: 32374

American (AMR) AF: 0.00 AC: 0 AN: 42730

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23868

East Asian (EAS) AF: 0.00 AC: 0 AN: 39556

South Asian (SAS) AF: 0.00 AC: 0 AN: 80960

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5296

European-Non Finnish (NFE) AF: 0.00000215 AC: 2 AN: 928662

Other (OTH) AF: 0.00 AC: 0 AN: 53484

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000180 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		0.37
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.12
Sift	Uncertain	0.010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.25	B
Vest4		0.36
MVP		0.25
MPC		0.099
ClinPred		0.64	D
GERP RS		2.0
Varity_R		0.24
gMVP		0.45
Mutation Taster		=91/9	polymorphism

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: rs139501061; hg19: chr1-25611169;