Variant X-119873266-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004541.4(NDUFA1):c.103-38T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0662 in 1,108,649 control chromosomes in the GnomAD database, including 2,224 homozygotes. There are 22,893 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.087 ( 408 hom., 2646 hem., cov: 21)

Exomes 𝑓: 0.064 ( 1816 hom. 20247 hem. )

Consequence

NDUFA1
NM_004541.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.556

Variant links:

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]

NDUFA1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant X-119873266-T-G is Benign according to our data. Variant chrX-119873266-T-G is described in ClinVar as [Benign]. Clinvar id is 1248855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA1	NM_004541.4 linkuse as main transcript	c.103-38T>G		intron_variant		ENST00000371437.5	NP_004532.1	O15239Q6IBB5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFA1	ENST00000371437.5 linkuse as main transcript	c.103-38T>G		intron_variant		1	NM_004541.4	ENSP00000360492.4		O15239

Frequencies

GnomAD3 genomes

AF:

0.0865

AC:

9582

AN:

110805

Hom.:

406

Cov.:

AF XY:

0.0799

AC XY:

2639

AN XY:

33023

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.00586

Gnomad AMR

AF:

0.0715

Gnomad ASJ

AF:

0.0530

Gnomad EAS

AF:

0.155

Gnomad SAS

AF:

0.0943

Gnomad FIN

AF:

0.0289

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.0556

Gnomad OTH

AF:

0.0941

GnomAD3 exomes

AF:

0.0784

AC:

14357

AN:

183064

Hom.:

489

AF XY:

0.0778

AC XY:

5251

AN XY:

67534

show subpopulations

Gnomad AFR exome

AF:

0.156

Gnomad AMR exome

AF:

0.0723

Gnomad ASJ exome

AF:

0.0531

Gnomad EAS exome

AF:

0.166

Gnomad SAS exome

AF:

0.109

Gnomad FIN exome

AF:

0.0322

Gnomad NFE exome

AF:

0.0572

Gnomad OTH exome

AF:

0.0812

GnomAD4 exome

AF:

0.0640

AC:

63827

AN:

997789

Hom.:

1816

Cov.:

AF XY:

0.0683

AC XY:

20247

AN XY:

296653

show subpopulations

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.0713

Gnomad4 ASJ exome

AF:

0.0531

Gnomad4 EAS exome

AF:

0.189

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.0343

Gnomad4 NFE exome

AF:

0.0530

Gnomad4 OTH exome

AF:

0.0786

GnomAD4 genome

AF:

0.0865

AC:

9592

AN:

110860

Hom.:

408

Cov.:

AF XY:

0.0800

AC XY:

2646

AN XY:

33088

show subpopulations

Gnomad4 AFR

AF:

0.152

Gnomad4 AMR

AF:

0.0713

Gnomad4 ASJ

AF:

0.0530

Gnomad4 EAS

AF:

0.154

Gnomad4 SAS

AF:

0.0938

Gnomad4 FIN

AF:

0.0289

Gnomad4 NFE

AF:

0.0556

Gnomad4 OTH

AF:

0.0943

Alfa

AF:

0.0406

Hom.:

310

Bravo

AF:

0.0964

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.0

DANN

Benign

0.70

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over