1-25301556-A-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PP3_StrongBS2_Supporting

The NM_016124.6(RHD):c.671A>C(p.Asn224Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000087 in 1,378,650 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000023 ( 0 hom., cov: 21)

Exomes 𝑓: 0.0000072 ( 2 hom. )

Consequence

RHD
NM_016124.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75

Publications

1 publications found

Variant links:

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]

RHD links:

RSRP1 (HGNC:25234): (arginine and serine rich protein 1)

RSRP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.977

BS2

High Homozygotes in GnomAdExome4 at 2 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RHD	NM_016124.6	MANE Select	c.671A>C	p.Asn224Thr	missense	Exon 5 of 10	NP_057208.3
RHD	NM_001282871.2		c.671A>C	p.Asn224Thr	missense	Exon 5 of 9	NP_001269800.1	Q02161-4
RHD	NM_001282870.1		c.671A>C	p.Asn224Thr	missense	Exon 5 of 9	NP_001269799.1	Q5XLT0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RHD	ENST00000328664.9	TSL:1 MANE Select	c.671A>C	p.Asn224Thr	missense	Exon 5 of 10	ENSP00000331871.4	Q02161-1
RHD	ENST00000342055.9	TSL:1	c.671A>C	p.Asn224Thr	missense	Exon 5 of 9	ENSP00000339577.5	Q02161-4
RHD	ENST00000568195.5	TSL:1	c.671A>C	p.Asn224Thr	missense	Exon 5 of 9	ENSP00000456966.1	H3BT10

Frequencies

GnomAD3 genomes

AF:

0.0000228

AC:

AN:

131504

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000262

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000360

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000444

AC:

AN:

225114

AF XY:

0.00

show subpopulations

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000722

AC:

AN:

1247146

Hom.:

Cov.:

AF XY:

0.00000322

AC XY:

AN XY:

622044

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31918

American (AMR)

AF:

0.00

AC:

AN:

42636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23792

East Asian (EAS)

AF:

0.00

AC:

AN:

39540

South Asian (SAS)

AF:

0.0000124

AC:

AN:

80546

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47068

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5256

European-Non Finnish (NFE)

AF:

0.00000867

AC:

AN:

923202

Other (OTH)

AF:

0.00

AC:

AN:

53188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000228

AC:

AN:

131504

Hom.:

Cov.:

AF XY:

0.0000311

AC XY:

AN XY:

64268

show subpopulations

African (AFR)

AF:

0.0000262

AC:

AN:

38124

American (AMR)

AF:

0.00

AC:

AN:

13610

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3128

East Asian (EAS)

AF:

0.00

AC:

AN:

5118

South Asian (SAS)

AF:

0.00

AC:

AN:

4378

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8764

Middle Eastern (MID)

AF:

0.00

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.0000360

AC:

AN:

55624

Other (OTH)

AF:

0.00

AC:

AN:

1816

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000885

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Uncertain

0.095

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.090

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.030

MetaRNN

Pathogenic

0.98

MetaSVM

Uncertain

0.24

MutationAssessor

Pathogenic

3.6

PhyloP100

5.7

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-5.6

REVEL

Pathogenic

0.69

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.83

MutPred

0.96

Loss of helix (P = 0.1299)

MVP

0.76

MPC

0.48

ClinPred

0.99

GERP RS

3.8

Varity_R

0.83

gMVP

0.86

Mutation Taster

=46/54

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over