Variant rs2305165 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001378107.1(R3HDM1):c.2000A>C(p.Gln667Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0994 in 1,604,660 control chromosomes in the GnomAD database, including 11,409 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1274 hom., cov: 32)

Exomes 𝑓: 0.098 ( 10135 hom. )

Consequence

R3HDM1
NM_001378107.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.97

Variant links:

Genes affected

R3HDM1 (HGNC:9757): (R3H domain containing 1) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

R3HDM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016035736).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
R3HDM1	NM_001378107.1 linkuse as main transcript	c.2000A>C	p.Gln667Pro	missense_variant	18/27	ENST00000683871.1	NP_001365036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
R3HDM1	ENST00000683871.1 linkuse as main transcript	c.2000A>C	p.Gln667Pro	missense_variant	18/27		NM_001378107.1	ENSP00000506980	A1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17657

AN:

152052

Hom.:

1278

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.0725

Gnomad AMR

AF:

0.195

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.167

Gnomad SAS

AF:

0.320

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.0838

Gnomad OTH

AF:

0.137

GnomAD3 exomes

AF:

0.140

AC:

33618

AN:

239464

Hom.:

3126

AF XY:

0.145

AC XY:

18750

AN XY:

129106

show subpopulations

Gnomad AFR exome

AF:

0.110

Gnomad AMR exome

AF:

0.204

Gnomad ASJ exome

AF:

0.114

Gnomad EAS exome

AF:

0.167

Gnomad SAS exome

AF:

0.296

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.0879

Gnomad OTH exome

AF:

0.134

GnomAD4 exome

AF:

0.0976

AC:

141831

AN:

1452490

Hom.:

10135

Cov.:

AF XY:

0.104

AC XY:

74882

AN XY:

721464

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.204

Gnomad4 ASJ exome

AF:

0.113

Gnomad4 EAS exome

AF:

0.172

Gnomad4 SAS exome

AF:

0.289

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.0733

Gnomad4 OTH exome

AF:

0.108

GnomAD4 genome

AF:

0.116

AC:

17662

AN:

152170

Hom.:

1274

Cov.:

AF XY:

0.123

AC XY:

9169

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.195

Gnomad4 ASJ

AF:

0.109

Gnomad4 EAS

AF:

0.168

Gnomad4 SAS

AF:

0.319

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.0838

Gnomad4 OTH

AF:

0.137

Alfa

AF:

0.0974

Hom.:

2091

Bravo

AF:

0.117

TwinsUK

AF:

0.0717

AC:

266

ALSPAC

AF:

0.0659

AC:

254

ESP6500AA

AF:

0.112

AC:

495

ESP6500EA

AF:

0.0829

AC:

713

ExAC

AF:

0.137

AC:

16625

Asia WGS

AF:

0.249

AC:

864

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.058

.;T;.;.;.

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

.;D;D;D;D

MetaRNN

Benign

0.0016

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

.;M;.;.;.

MutationTaster

Benign

0.00091

P;P;P;P;P

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.6

N;N;N;.;N

REVEL

Benign

0.16

Sift

Uncertain

0.0020

D;D;D;.;D

Sift4G

Benign

0.17

T;T;T;T;T

Polyphen

1.0

.;D;.;.;.

Vest4

0.35

MPC

0.39

ClinPred

0.065

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.33

gMVP

0.52

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over