Variant 19-901511-C-T 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 NM_138774.4(R3HDM4):c.262G>A(p.Gly88Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000189 in 1,608,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

R3HDM4
NM_138774.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.84

Variant links:

Genes affected

R3HDM4 (HGNC:28270): (R3H domain containing 4) Predicted to enable nucleic acid binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

R3HDM4 links:

R3HDM4 (HGNC:):

R3HDM4 links:

Genome browser will be placed here

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=0.026842743).

BP6

Variant 19-901511-C-T is Benign according to our data. Variant chr19-901511-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3150519.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
R3HDM4	NM_138774.4 linkuse as main transcript	c.262G>A	p.Gly88Ser	missense_variant	3/8	ENST00000361574.10	NP_620129.2	Q96D70
R3HDM4	XM_011528416.3 linkuse as main transcript	c.262G>A	p.Gly88Ser	missense_variant	3/8		XP_011526718.1
R3HDM4	XM_024451771.2 linkuse as main transcript	c.-105G>A		5_prime_UTR_variant	3/8		XP_024307539.1
R3HDM4	XM_047439659.1 linkuse as main transcript	c.-16+465G>A		intron_variant			XP_047295615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
R3HDM4	ENST00000361574.10 linkuse as main transcript	c.262G>A	p.Gly88Ser	missense_variant	3/8	1	NM_138774.4	ENSP00000355385.4		Q96D70

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000221

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000103

AC:

AN:

243018

Hom.:

AF XY:

0.0000759

AC XY:

AN XY:

131824

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000262

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000109

Gnomad NFE exome

AF:

0.000118

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.000193

AC:

281

AN:

1456126

Hom.:

Cov.:

AF XY:

0.000181

AC XY:

131

AN XY:

724306

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000123

Gnomad4 NFE exome

AF:

0.000230

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000151

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000271

Hom.:

Bravo

AF:

0.000193

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000660

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000237

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

Jan 17, 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

0.062

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.013

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.027

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.

PrimateAI

Benign

0.37

PROVEAN

Benign

0.75

N;.

REVEL

Benign

0.071

Sift

Benign

0.58

T;.

Sift4G

Benign

0.52

T;T

Polyphen

0.072

B;.

Vest4

0.18

MVP

0.14

MPC

0.15

ClinPred

0.024

GERP RS

-0.15

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.030

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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