X-119870595-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006978.3(RNF113A):​c.1019T>G​(p.Ile340Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Consequence

RNF113A
NM_006978.3 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.222
Variant links:
Genes affected
RNF113A (HGNC:12974): (ring finger protein 113A) This intronless gene encodes a protein which contains a C3H1-type zinc finger domain and a C3HC4 Ring-type (Really Interesting New Gene-type) zinc finger domain. The Ring-type zinc finger domain is identified in various tumor suppressors, DNA repair genes and cytokine receptor-associated molecules, and is probably involved in mediating protein-protein interactions. [provided by RefSeq, May 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07216388).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RNF113ANM_006978.3 linkuse as main transcriptc.1019T>G p.Ile340Ser missense_variant 1/1 ENST00000371442.4 NP_008909.1 O15541

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RNF113AENST00000371442.4 linkuse as main transcriptc.1019T>G p.Ile340Ser missense_variant 1/16 NM_006978.3 ENSP00000360497.2 O15541

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
22

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxJun 14, 2022Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
15
DANN
Benign
0.55
DEOGEN2
Benign
0.0061
T
FATHMM_MKL
Benign
0.063
N
LIST_S2
Benign
0.51
T
M_CAP
Benign
0.0027
T
MetaRNN
Benign
0.072
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.8
L
PrimateAI
Benign
0.36
T
PROVEAN
Benign
0.67
N
REVEL
Benign
0.079
Sift
Uncertain
0.011
D
Sift4G
Benign
0.74
T
Polyphen
0.0010
B
Vest4
0.29
MutPred
0.25
Gain of glycosylation at I340 (P = 0.005);
MVP
0.36
MPC
1.3
ClinPred
0.062
T
GERP RS
-1.6
Varity_R
0.062
gMVP
0.40

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: chrX-119004558; API