rs794726863

Variant names:

• chrX-119870713-G-A
• rs794726863
• NM_006978.3:c.901C>T

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_006978.3(RNF113A):​c.901C>T​(p.Gln301*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: RNF113A NM_006978.3 stop_gained
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 2.51
• Publications: 6 publications found

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]

RNF113A Gene-Disease associations (from GenCC):

• trichothiodystrophy 5, nonphotosensitive

  Inheritance: XL Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Genomics England PanelApp, Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• trichothiodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000297015 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 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 0.127 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-119870713-G-A is Pathogenic according to our data. Variant chrX-119870713-G-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 192382.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006978.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF113A	NM_006978.3	MANE Select	c.901C>T	p.Gln301*	stop_gained	Exon 1 of 1	NP_008909.1	O15541

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF113A	ENST00000371442.4	TSL:6 MANE Select	c.901C>T	p.Gln301*	stop_gained	Exon 1 of 1	ENSP00000360497.2	O15541
	ENSG00000297015	ENST00000744274.1		n.261+12118C>T		intron	N/A
	ENSG00000297015	ENST00000744275.1		n.163-16994C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	not provided (1)
1	-	-	Trichothiodystrophy 5, nonphotosensitive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.74	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	37
DANN	Uncertain	1.0
FATHMM_MKL	Uncertain	0.84	D
PhyloP100		2.5
Vest4		0.20
GERP RS		5.8
Mutation Taster		=1/199	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs794726863; hg19: chrX-119004676;