Genetic Variant NM_001394031.1:c.1903G>T (chr12-57268430-C-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_001394031.1(R3HDM2):c.1903G>T(p.Val635Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V635M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

R3HDM2
NM_001394031.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.53

Publications

1 publications found

Variant links:

Genes affected

R3HDM2 (HGNC:29167): (R3H domain containing 2) Enables RNA binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

R3HDM2 links:

ENSG00000258830 (HGNC:):

ENSG00000258830 links:

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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=0.28522068).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394031.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
R3HDM2	NM_001394031.1	MANE Select	c.1903G>T	p.Val635Leu	missense	Exon 18 of 24	NP_001380960.1	B5MCU0
R3HDM2	NM_001351204.2		c.2059G>T	p.Val687Leu	missense	Exon 20 of 26	NP_001338133.1
R3HDM2	NM_001351205.2		c.2059G>T	p.Val687Leu	missense	Exon 19 of 25	NP_001338134.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
R3HDM2	ENST00000402412.6	TSL:1 MANE Select	c.1903G>T	p.Val635Leu	missense	Exon 18 of 24	ENSP00000385839.1	B5MCU0
R3HDM2	ENST00000347140.7	TSL:1	c.1861G>T	p.Val621Leu	missense	Exon 18 of 24	ENSP00000317903.6	Q9Y2K5-1
R3HDM2	ENST00000393811.6	TSL:1	n.1697G>T		non_coding_transcript_exon	Exon 8 of 14

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251136

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111998

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.021

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.012

MetaRNN

Benign

0.29

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

5.5

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.92

REVEL

Benign

0.14

Sift

Benign

0.17

Sift4G

Benign

0.56

Polyphen

0.99

Vest4

0.75

MutPred

0.15

Gain of glycosylation at P659 (P = 0.1801)

MVP

0.30

MPC

0.68

ClinPred

0.82

GERP RS

4.6

Varity_R

0.23

gMVP

0.32

Mutation Taster

=69/31

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over