chrX-119873028-A-G

Position:

• chrX-119873028-A-G

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.103-276A>G 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 0.087 (405 hom., 2366 hem., cov: 20)
• Consequence: NDUFA1 NM_004541.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.192

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=-1.01).
• BP6: Variant X-119873028-A-G is Benign according to our data. Variant chrX-119873028-A-G is described in ClinVar as [Benign]. Clinvar id is 1237407.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA1	NM_004541.4	c.103-276A>G		intron_variant		ENST00000371437.5	NP_004532.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA1	ENST00000371437.5	c.103-276A>G		intron_variant		1	NM_004541.4	ENSP00000360492.4

Frequencies

GnomAD3 genomes AF: 0.0866 AC: 9220 AN: 106429 Hom.: 403 Cov.: 20 AF XY: 0.0805 AC XY: 2361 AN XY: 29313

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.00593

Gnomad AMR AF: 0.0721

Gnomad ASJ AF: 0.0537

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0254

Gnomad MID AF: 0.181

Gnomad NFE AF: 0.0554

Gnomad OTH AF: 0.0989

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

GnomAD4 genome AF: 0.0867 AC: 9228 AN: 106450 Hom.: 405 Cov.: 20 AF XY: 0.0806 AC XY: 2366 AN XY: 29350

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.0719

Gnomad4 ASJ AF: 0.0537

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0254

Gnomad4 NFE AF: 0.0554

Gnomad4 OTH AF: 0.0993

Alfa AF: 0.0600 Hom.: 3801

Bravo AF: 0.0964

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

Jun 28, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.0
DANN	Benign	0.48

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: rs5910697; hg19: chrX-119006991;