chrX-119873060-T-A

Position:

• chrX-119873060-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004541.4(NDUFA1):​c.103-244T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.44 (7699 hom., 10474 hem., cov: 18)
• Consequence: NDUFA1 NM_004541.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.89

Genes affected

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant X-119873060-T-A is Benign according to our data. Variant chrX-119873060-T-A is described in ClinVar as [Benign]. Clinvar id is 1178983.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFA1	NM_004541.4	c.103-244T>A		intron_variant		ENST00000371437.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFA1	ENST00000371437.5	c.103-244T>A		intron_variant		1	NM_004541.4	P1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 43789 AN: 100414 Hom.: 7704 Cov.: 18 AF XY: 0.414 AC XY: 10451 AN XY: 25242

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.422

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.436 AC: 43797 AN: 100426 Hom.: 7699 Cov.: 18 AF XY: 0.414 AC XY: 10474 AN XY: 25272

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.654

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.452

Alfa AF: 0.392 Hom.: 2166

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.59
DANN	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs2428220; hg19: chrX-119007023;