Genetic Variant RHCG:p.Gly383Arg (chr15-89477172-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_016321.3(RHCG):c.1147G>A(p.Gly383Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,892 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

RHCG
NM_016321.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.40

Publications

0 publications found

Variant links:

Genes affected

RHCG (HGNC:18140): (Rh family C glycoprotein) Enables ammonium transmembrane transporter activity; ankyrin binding activity; and identical protein binding activity. Involved in ammonium transmembrane transport; cellular ion homeostasis; and transepithelial ammonium transport. Located in apical plasma membrane and basolateral plasma membrane. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RHCG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 15-89477172-C-T is Benign according to our data. Variant chr15-89477172-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2363760.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016321.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RHCG	NM_016321.3	MANE Select	c.1147G>A	p.Gly383Arg	missense	Exon 8 of 11	NP_057405.1	Q9UBD6
RHCG	NM_001321041.2		c.1147G>A	p.Gly383Arg	missense	Exon 8 of 11	NP_001307970.1	Q9UBD6
RHCG	NR_110261.2		n.1110G>A		non_coding_transcript_exon	Exon 8 of 11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RHCG	ENST00000268122.9	TSL:1 MANE Select	c.1147G>A	p.Gly383Arg	missense	Exon 8 of 11	ENSP00000268122.4	Q9UBD6
RHCG	ENST00000560081.5	TSL:1	n.*75G>A		non_coding_transcript_exon	Exon 8 of 11	ENSP00000453588.1	H0YMF8
RHCG	ENST00000560081.5	TSL:1	n.*75G>A		3_prime_UTR	Exon 8 of 11	ENSP00000453588.1	H0YMF8

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000795

AC:

AN:

251454

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

1111996

Other (OTH)

AF:

0.0000497

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152022

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41390

American (AMR)

AF:

0.0000655

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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:

0.0000564

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.079

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.014

(source)

DANN

Benign

0.47

DEOGEN2

Benign

0.22

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.0097

LIST_S2

Benign

0.22

M_CAP

Benign

0.0028

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

-3.4

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.0

REVEL

Benign

0.20

Sift

Benign

0.14

Sift4G

Benign

0.42

Polyphen

0.070

Vest4

0.19

MutPred

0.78

Gain of MoRF binding (P = 0.0781)

MVP

0.14

MPC

0.25

ClinPred

0.086

GERP RS

-11

Varity_R

0.13

gMVP

0.63

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: -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