dbSNP rs746911206: RTP5:p.Arg88His (chr2-241871818-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_173821.3(RTP5):c.263G>A(p.Arg88His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,564,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R88C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000092 ( 0 hom. )

Consequence

RTP5
NM_173821.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.313

Publications

2 publications found

Variant links:

Genes affected

RTP5 (HGNC:26585): (receptor transporter protein 5 (putative)) Predicted to enable olfactory receptor binding activity. Predicted to be involved in detection of chemical stimulus involved in sensory perception of bitter taste; protein insertion into membrane; and protein targeting to membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

RTP5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35585508).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173821.3. 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
	RTP5	NM_173821.3	MANE Select	c.263G>A	p.Arg88His	missense	Exon 2 of 2	NP_776182.2	Q14D33

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RTP5	ENST00000343216.3	TSL:1 MANE Select	c.263G>A	p.Arg88His	missense	Exon 2 of 2	ENSP00000345374.3	Q14D33
RTP5	ENST00000419912.1	TSL:5	n.*276G>A		non_coding_transcript_exon	Exon 3 of 3	ENSP00000397191.1	F8WB75
RTP5	ENST00000419912.1	TSL:5	n.*276G>A		3_prime_UTR	Exon 3 of 3	ENSP00000397191.1	F8WB75

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000116

AC:

AN:

172558

AF XY:

0.0000107

show subpopulations

Gnomad AFR exome

AF:

0.0000994

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:

0.0000137

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000921

AC:

AN:

1412174

Hom.:

Cov.:

AF XY:

0.0000143

AC XY:

AN XY:

698300

show subpopulations

African (AFR)

AF:

0.0000309

AC:

AN:

32350

American (AMR)

AF:

0.00

AC:

AN:

36596

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24478

East Asian (EAS)

AF:

0.00

AC:

AN:

37518

South Asian (SAS)

AF:

0.00

AC:

AN:

80166

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5656

European-Non Finnish (NFE)

AF:

0.0000110

AC:

AN:

1087702

Other (OTH)

AF:

0.00

AC:

AN:

58306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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:

152174

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.000101

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000168

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

Uncertain

0.39

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

Eigen

Benign

0.057

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.66

M_CAP

Benign

0.0049

MetaRNN

Benign

0.36

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

PhyloP100

-0.31

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-4.8

REVEL

Benign

0.14

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.34

MVP

0.15

MPC

0.70

ClinPred

0.95

GERP RS

2.8

Varity_R

0.58

gMVP

0.68

Mutation Taster

=92/8

polymorphism

(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

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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