rs459894

Positions:

• chr16-23590167-A-G
• chr16-23590167-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005003.3(NDUFAB1):​c.169-2848T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,180 control chromosomes in the GnomAD database, including 1,254 homozygotes. 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 0.12 (1254 hom., cov: 31)
• Consequence: NDUFAB1 NM_005003.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFAB1	NM_005003.3	c.169-2848T>C		intron_variant		ENST00000007516.8	NP_004994.1
NDUFAB1	XM_011545856.3	c.261+926T>C		intron_variant			XP_011544158.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFAB1	ENST00000007516.8	c.169-2848T>C		intron_variant		1	NM_005003.3	ENSP00000007516	P1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18216 AN: 152062 Hom.: 1244 Cov.: 31

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0849

Gnomad ASJ AF: 0.0646

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.0975

Gnomad FIN AF: 0.0991

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0887

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.120 AC: 18256 AN: 152180 Hom.: 1254 Cov.: 31 AF XY: 0.119 AC XY: 8873 AN XY: 74392

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.0847

Gnomad4 ASJ AF: 0.0646

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.0969

Gnomad4 FIN AF: 0.0991

Gnomad4 NFE AF: 0.0887

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0885 Hom.: 1017

Bravo AF: 0.123

Asia WGS AF: 0.132 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.89
DANN	Benign	0.78

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: rs459894; hg19: chr16-23601488;