Variant 19-902059-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138774.4(R3HDM4):c.143A>G(p.Gln48Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,758 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

R3HDM4
NM_138774.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.60

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
R3HDM4	NM_138774.4 linkuse as main transcript	c.143A>G	p.Gln48Arg	missense_variant	2/8	ENST00000361574.10	NP_620129.2
R3HDM4	XM_011528416.3 linkuse as main transcript	c.143A>G	p.Gln48Arg	missense_variant	2/8		XP_011526718.1
R3HDM4	XM_024451771.2 linkuse as main transcript	c.-224A>G		5_prime_UTR_variant	2/8		XP_024307539.1
R3HDM4	XM_047439659.1 linkuse as main transcript	c.-99A>G		5_prime_UTR_variant	2/7		XP_047295615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
R3HDM4	ENST00000361574.10 linkuse as main transcript	c.143A>G	p.Gln48Arg	missense_variant	2/8	1	NM_138774.4	ENSP00000355385	P1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461562

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 03, 2024

The c.143A>G (p.Q48R) alteration is located in exon 2 (coding exon 2) of the R3HDM4 gene. This alteration results from a A to G substitution at nucleotide position 143, causing the glutamine (Q) at amino acid position 48 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

0.0094

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

T;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.082

MetaRNN

Uncertain

0.45

T;T

MetaSVM

Benign

-0.61

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.78

N;.

REVEL

Benign

0.18

Sift

Benign

0.14

T;.

Sift4G

Uncertain

0.048

D;T

Polyphen

0.95

P;.

Vest4

0.64

MutPred

0.19

Gain of helix (P = 0.0696);.;

MVP

0.49

MPC

0.60

ClinPred

0.47

GERP RS

4.7

Varity_R

0.22

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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