rs558832446

Variant summary

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

The NM_001100588.3(RC3H2):​c.3149A>T​(p.Asp1050Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,852 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. D1050G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RC3H2
NM_001100588.3 missense

Scores

1
7
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.06
Variant links:
Genes affected
RC3H2 (HGNC:21461): (ring finger and CCCH-type domains 2) Enables nucleic acid binding activity and ubiquitin protein ligase activity. Involved in protein polyubiquitination. Located in cell surface; intracellular membrane-bounded organelle; and membrane. [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
RC3H2NM_001100588.3 linkc.3149A>T p.Asp1050Val missense_variant Exon 19 of 21 ENST00000357244.7 NP_001094058.1
RC3H2NM_001354479.2 linkc.2978A>T p.Asp993Val missense_variant Exon 18 of 20 NP_001341408.1
RC3H2NM_001354478.2 linkc.3149A>T p.Asp1050Val missense_variant Exon 19 of 21 NP_001341407.1
RC3H2NM_001354482.2 linkc.3118-176A>T intron_variant Intron 18 of 19 NP_001341411.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RC3H2ENST00000357244.7 linkc.3149A>T p.Asp1050Val missense_variant Exon 19 of 21 5 NM_001100588.3 ENSP00000349783.2 Q9HBD1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461852
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727224
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:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.0029
T
BayesDel_noAF
Benign
-0.24
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.058
T;T
Eigen
Uncertain
0.23
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
.;D
M_CAP
Benign
0.037
D
MetaRNN
Uncertain
0.69
D;D
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.55
N;N
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.27
Sift4G
Uncertain
0.0070
D;D
Polyphen
1.0
D;D
Vest4
0.75
MutPred
0.39
Loss of solvent accessibility (P = 0.0299);Loss of solvent accessibility (P = 0.0299);
MVP
0.63
MPC
0.93
ClinPred
0.85
D
GERP RS
5.7
Varity_R
0.44
gMVP
0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-125613684; API