16-23590167-A-T

Variant names:

• chr16-23590167-A-T
• rs459894
• NM_005003.3:c.169-2848T>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005003.3(NDUFAB1):​c.169-2848T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 152,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000066 (0 hom., cov: 31)
• Consequence: NDUFAB1 NM_005003.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309
• Publications: 13 publications found

Genes affected

NDUFAB1 (HGNC:7694): (NADH:ubiquinone oxidoreductase subunit AB1) Predicted to enable acyl binding activity; acyl carrier activity; and fatty acid binding activity. Involved in mitochondrial respiratory chain complex I assembly and protein lipoylation. Located in mitochondrion and nucleoplasm. Part of mitochondrial respiratory chain complex I. Colocalizes with mitochondrial large ribosomal subunit. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFAB1	NM_005003.3	c.169-2848T>A		intron_variant	Intron 1 of 4	ENST00000007516.8	NP_004994.1
NDUFAB1	XM_011545856.3	c.261+926T>A		intron_variant	Intron 2 of 5		XP_011544158.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFAB1	ENST00000007516.8	c.169-2848T>A		intron_variant	Intron 1 of 4	1	NM_005003.3	ENSP00000007516.2

Frequencies

GnomAD3 genomes AF: 0.0000658 AC: 10 AN: 152088 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152206 Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 8 AN XY: 74412

African (AFR) AF: 0.00 AC: 0 AN: 41514

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 2027

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.77
DANN	Benign	0.86
PhyloP100		-0.31

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

Other links and lift over

dbSNP: rs459894; hg19: chr16-23601488;