X-119870722-CAT-C

Position:

• chrX-119870722-CAT-C

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_006978.3(RNF113A):​c.890_891delAT​(p.Tyr297fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: RNF113A NM_006978.3 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.22

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.138 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-119870722-CAT-C is Pathogenic according to our data. Variant chrX-119870722-CAT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2578338.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF113A	NM_006978.3	c.890_891delAT	p.Tyr297fs	frameshift_variant	1/1	ENST00000371442.4	NP_008909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF113A	ENST00000371442.4	c.890_891delAT	p.Tyr297fs	frameshift_variant	1/1	6	NM_006978.3	ENSP00000360497.2

Frequencies

GnomAD3 genomes Cov.: 23

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Trichothiodystrophy 5, nonphotosensitive Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Clinical Genetics Laboratory, Exon Genomics

Sep 01, 2023

The Tyr297Cysfs*3 variant was observed in a child with short stature, dry-skin, sparse hair and global developmental delay. It is a Null variant (frame-shift), predicted to cause NMD. Loss-of-function is a known mechanism of disease (gene has 3 reported pathogenic LOF variants). It is also absent from controls. In summary, the Tyr297Cysfs*3 variant meets ACMG criteria to be classified as pathogenic. -

Computational scores

Source: dbNSFP v4.3

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: chrX-119004685;