rs1800823

Variant names:

• chrX-119871624-T-C
• rs1800823
• NM_006978.3:c.-11A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006978.3(RNF113A):​c.-11A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0661 in 1,170,794 control chromosomes in the GnomAD database, including 2,284 homozygotes. There are 25,433 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.088 (416 hom., 2928 hem., cov: 24)
  • Exomes 𝑓: 0.064 (1868 hom. 22505 hem.)
• Consequence: RNF113A NM_006978.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.50

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]

NDUFA1 (HGNC:7683): (NADH:ubiquinone oxidoreductase subunit A1) The human NDUFA1 gene codes for an essential component of complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone. It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha-helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and might act as an anchor for the NADH:ubiquinone oxidoreductase complex at the inner mitochondrial membrane. However, the NDUFA1 peptide is one of about 31 components of the "hydrophobic protein" (HP) fraction of complex I which is involved in proton translocation. Thus the NDUFA1 peptide may also participate in that function. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant X-119871624-T-C is Benign according to our data. Variant chrX-119871624-T-C is described in ClinVar as [Benign]. Clinvar id is 1229614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF113A	NM_006978.3	c.-11A>G		5_prime_UTR_variant	Exon 1 of 1	ENST00000371442.4	NP_008909.1
NDUFA1	NM_004541.4	c.-288T>C		upstream_gene_variant		ENST00000371437.5	NP_004532.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF113A	ENST00000371442.4	c.-11A>G		5_prime_UTR_variant	Exon 1 of 1	6	NM_006978.3	ENSP00000360497.2
NDUFA1	ENST00000371437.5	c.-288T>C		upstream_gene_variant		1	NM_004541.4	ENSP00000360492.4

Frequencies

GnomAD3 genomes AF: 0.0884 AC: 9984 AN: 112956 Hom.: 414 Cov.: 24 AF XY: 0.0832 AC XY: 2922 AN XY: 35114

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.00584

Gnomad AMR AF: 0.0727

Gnomad ASJ AF: 0.0527

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.0938

Gnomad FIN AF: 0.0301

Gnomad MID AF: 0.176

Gnomad NFE AF: 0.0562

Gnomad OTH AF: 0.0975

GnomAD3 exomes AF: 0.0806 AC: 11726 AN: 145425 Hom.: 427 AF XY: 0.0788 AC XY: 3739 AN XY: 47453

Gnomad AFR exome AF: 0.161

Gnomad AMR exome AF: 0.0771

Gnomad ASJ exome AF: 0.0531

Gnomad EAS exome AF: 0.169

Gnomad SAS exome AF: 0.113

Gnomad FIN exome AF: 0.0325

Gnomad NFE exome AF: 0.0575

Gnomad OTH exome AF: 0.0825

GnomAD4 exome AF: 0.0638 AC: 67444 AN: 1057784 Hom.: 1868 Cov.: 31 AF XY: 0.0662 AC XY: 22505 AN XY: 340030

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.0755

Gnomad4 ASJ exome AF: 0.0539

Gnomad4 EAS exome AF: 0.189

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.0343

Gnomad4 NFE exome AF: 0.0532

Gnomad4 OTH exome AF: 0.0788

GnomAD4 genome AF: 0.0884 AC: 9993 AN: 113010 Hom.: 416 Cov.: 24 AF XY: 0.0832 AC XY: 2928 AN XY: 35178

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.0725

Gnomad4 ASJ AF: 0.0527

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.0934

Gnomad4 FIN AF: 0.0301

Gnomad4 NFE AF: 0.0562

Gnomad4 OTH AF: 0.0976

Alfa AF: 0.0696 Hom.: 2209

Bravo AF: 0.0986

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Trichothiodystrophy 5, nonphotosensitive Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.2
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs1800823; hg19: chrX-119005587; COSMIC: COSV65097469;