X-119873071-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004541.4(NDUFA1):c.103-225del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.013 (25 hom., 286 hem., cov: 20)
• Consequence: NDUFA1 NM_004541.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.121

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 -10 ACMG points.

• BP6: Variant X-119873071-GA-G is Benign according to our data. Variant chrX-119873071-GA-G is described in ClinVar as [Likely_benign]. Clinvar id is 1218732.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0129 (1312/101497) while in subpopulation AFR AF= 0.0413 (1136/27499). AF 95% confidence interval is 0.0393. There are 25 homozygotes in gnomad4. There are 286 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 24 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFA1	NM_004541.4	c.103-225del		intron_variant		ENST00000371437.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFA1	ENST00000371437.5	c.103-225del		intron_variant		1	NM_004541.4	P1

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1309 AN: 101468 Hom.: 24 Cov.: 20 AF XY: 0.0108 AC XY: 286 AN XY: 26518

Gnomad AFR AF: 0.0413

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00486

Gnomad ASJ AF: 0.000797

Gnomad EAS AF: 0.000603

Gnomad SAS AF: 0.000445

Gnomad FIN AF: 0.000233

Gnomad MID AF: 0.00448

Gnomad NFE AF: 0.00211

Gnomad OTH AF: 0.0126

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

GnomAD4 genome AF: 0.0129 AC: 1312 AN: 101497 Hom.: 25 Cov.: 20 AF XY: 0.0108 AC XY: 286 AN XY: 26561

Gnomad4 AFR AF: 0.0413

Gnomad4 AMR AF: 0.00486

Gnomad4 ASJ AF: 0.000797

Gnomad4 EAS AF: 0.000605

Gnomad4 SAS AF: 0.000894

Gnomad4 FIN AF: 0.000233

Gnomad4 NFE AF: 0.00211

Gnomad4 OTH AF: 0.0125

Alfa AF: 0.000499 Hom.: 3

Asia WGS AF: 0.00401 AC: 10 AN: 2504

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 18, 2020

- -

Computational scores

Source: dbNSFP v4.3

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: rs201390495; hg19: chrX-119007034;