X-119873061-A-T

Position:

• chrX-119873061-A-T

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.103-243A>T 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 0.097 (364 hom., 2071 hem., cov: 18)
• Consequence: NDUFA1 NM_004541.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.111

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=-0.98).
• BP6: Variant X-119873061-A-T is Benign according to our data. Variant chrX-119873061-A-T is described in ClinVar as [Benign]. Clinvar id is 1259573.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA1	NM_004541.4	c.103-243A>T		intron_variant		ENST00000371437.5	NP_004532.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA1	ENST00000371437.5	c.103-243A>T		intron_variant		1	NM_004541.4	ENSP00000360492.4

Frequencies

GnomAD3 genomes AF: 0.0973 AC: 8255 AN: 84882 Hom.: 364 Cov.: 18 AF XY: 0.0896 AC XY: 2070 AN XY: 23114

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.00161

Gnomad AMR AF: 0.0761

Gnomad ASJ AF: 0.0633

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0276

Gnomad MID AF: 0.154

Gnomad NFE AF: 0.0514

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.0973 AC: 8257 AN: 84888 Hom.: 364 Cov.: 18 AF XY: 0.0895 AC XY: 2071 AN XY: 23132

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.0759

Gnomad4 ASJ AF: 0.0633

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.0276

Gnomad4 NFE AF: 0.0514

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0718 Hom.: 222

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 26, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.81
DANN	Benign	0.15

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: rs5910698; hg19: chrX-119007024;