rs147536237

Variant summary

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

The NM_001378107.1(R3HDM1):​c.1430C>G​(p.Ala477Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A477V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.000012 ( 0 hom. )

Consequence

R3HDM1
NM_001378107.1 missense

Scores

1
7
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.07
Variant links:
Genes affected
R3HDM1 (HGNC:9757): (R3H domain containing 1) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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 rank MANE Protein UniProt
R3HDM1NM_001378107.1 linkc.1430C>G p.Ala477Gly missense_variant Exon 15 of 27 ENST00000683871.1 NP_001365036.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
R3HDM1ENST00000683871.1 linkc.1430C>G p.Ala477Gly missense_variant Exon 15 of 27 NM_001378107.1 ENSP00000506980.1 A0A804HIA8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000358
AC:
9
AN:
251336
Hom.:
0
AF XY:
0.0000663
AC XY:
9
AN XY:
135842
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000792
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1461804
Hom.:
0
Cov.:
30
AF XY:
0.0000165
AC XY:
12
AN XY:
727208
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000151
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000741
AC:
9

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.21
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.038
T;.;.
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.82
T;T;T
M_CAP
Benign
0.012
T
MetaRNN
Uncertain
0.47
T;T;T
MetaSVM
Benign
-0.55
T
MutationAssessor
Uncertain
2.6
M;.;M
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-2.2
N;N;N
REVEL
Benign
0.22
Sift
Uncertain
0.0060
D;D;D
Sift4G
Benign
0.15
T;T;T
Polyphen
1.0
D;.;.
Vest4
0.66
MVP
0.66
MPC
0.85
ClinPred
0.37
T
GERP RS
5.7
Varity_R
0.38
gMVP
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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.

Other links and lift over

dbSNP: rs147536237; hg19: chr2-136399316; API