Variant 8-23290315-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000265806.12(R3HCC1):c.698G>A(p.Arg233Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000572 in 1,399,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

R3HCC1
ENST00000265806.12 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0210

Variant links:

Genes affected

R3HCC1 (HGNC:27329): (R3H domain and coiled-coil containing 1) Predicted to enable nucleic acid binding activity. [provided by Alliance of Genome Resources, Apr 2022]

R3HCC1 links:

R3HCC1 (HGNC:):

R3HCC1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0278337).

BP6

Variant 8-23290315-G-A is Benign according to our data. Variant chr8-23290315-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3150469.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
R3HCC1	NM_001136108.3 linkuse as main transcript	c.698G>A	p.Arg233Gln	missense_variant	4/8	ENST00000265806.12	NP_001129580.2	Q9Y3T6-1
R3HCC1	NM_001301650.2 linkuse as main transcript	c.572G>A	p.Arg191Gln	missense_variant	5/9		NP_001288579.1	Q9Y3T6-3
R3HCC1	NR_125897.1 linkuse as main transcript	n.687-20G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
R3HCC1	ENST00000265806.12 linkuse as main transcript	c.698G>A	p.Arg233Gln	missense_variant	4/8	1	NM_001136108.3	ENSP00000265806.8		Q9Y3T6-1A0A0R4J2E2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000389

AC:

AN:

154318

Hom.:

AF XY:

0.0000611

AC XY:

AN XY:

81884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000458

Gnomad SAS exome

AF:

0.0000439

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000572

AC:

AN:

1399464

Hom.:

Cov.:

AF XY:

0.0000101

AC XY:

AN XY:

690248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000839

Gnomad4 SAS exome

AF:

0.0000379

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000185

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.28

DANN

Benign

0.23

DEOGEN2

Benign

0.0026

T;.;.;.;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0071

LIST_S2

Benign

0.61

T;T;.;T;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.028

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.18

PROVEAN

Benign

-2.0

.;N;N;.;.

REVEL

Benign

0.033

Sift

Benign

0.12

.;T;T;.;.

Sift4G

Benign

1.0

T;T;T;T;T

Vest4

0.071

MutPred

0.16

.;.;Loss of MoRF binding (P = 0.0494);.;.;

MVP

0.014

ClinPred

0.025

GERP RS

-3.1

gMVP

0.093

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over