rs1800823

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000371442.4(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 ENST00000371442.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.50
• 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]

ENSG00000297015 (HGNC:):

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]

NDUFA1 Gene-Disease associations (from GenCC):

• mitochondrial complex I deficiency, nuclear type 12

  Inheritance: XL, AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Leigh syndrome

  Inheritance: XL Classification: MODERATE Submitted by: ClinGen
• mitochondrial complex I deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000371442.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF113A	NM_006978.3	MANE Select	c.-11A>G		5_prime_UTR	Exon 1 of 1	NP_008909.1
	NDUFA1	NM_004541.4	MANE Select	c.-288T>C		upstream_gene	N/A	NP_004532.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF113A	ENST00000371442.4	TSL:6 MANE Select	c.-11A>G		5_prime_UTR	Exon 1 of 1	ENSP00000360497.2
	ENSG00000297015	ENST00000744274.1		n.261+11207A>G		intron	N/A
	ENSG00000297015	ENST00000744275.1		n.163-17905A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0884 AC: 9984 AN: 112956 Hom.: 414 Cov.: 24

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

GnomAD2 exomes AF: 0.0806 AC: 11726 AN: 145425 AF XY: 0.0788

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 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

African (AFR) AF: 0.163 AC: 4077 AN: 24950

American (AMR) AF: 0.0755 AC: 2158 AN: 28596

Ashkenazi Jewish (ASJ) AF: 0.0539 AC: 898 AN: 16653

East Asian (EAS) AF: 0.189 AC: 5665 AN: 29896

South Asian (SAS) AF: 0.115 AC: 5536 AN: 47960

European-Finnish (FIN) AF: 0.0343 AC: 1331 AN: 38749

Middle Eastern (MID) AF: 0.141 AC: 552 AN: 3914

European-Non Finnish (NFE) AF: 0.0532 AC: 43742 AN: 822844

Other (OTH) AF: 0.0788 AC: 3485 AN: 44222

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

African (AFR) AF: 0.156 AC: 4866 AN: 31155

American (AMR) AF: 0.0725 AC: 782 AN: 10785

Ashkenazi Jewish (ASJ) AF: 0.0527 AC: 140 AN: 2657

East Asian (EAS) AF: 0.157 AC: 562 AN: 3584

South Asian (SAS) AF: 0.0934 AC: 262 AN: 2806

European-Finnish (FIN) AF: 0.0301 AC: 188 AN: 6254

Middle Eastern (MID) AF: 0.184 AC: 40 AN: 217

European-Non Finnish (NFE) AF: 0.0562 AC: 2999 AN: 53330

Other (OTH) AF: 0.0976 AC: 150 AN: 1537

Alfa AF: 0.0729 Hom.: 3083

Bravo AF: 0.0986

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Trichothiodystrophy 5, nonphotosensitive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.2
DANN	Benign	0.75
PhyloP100		-2.5
PromoterAI		0.051	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=298/2	polymorphism (auto)

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

Other links and lift over

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