rs466719

Positions:

• chr16-23596183-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005003.3(NDUFAB1):​c.108C>G​(p.Leu36=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0819 in 1,610,830 control chromosomes in the GnomAD database, including 6,276 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 0.11 (1049 hom., cov: 33)
  • Exomes 𝑓: 0.079 (5227 hom.)
• Consequence: NDUFAB1 NM_005003.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.444

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP7: Synonymous conserved (PhyloP=-0.444 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFAB1	NM_005003.3	c.108C>G	p.Leu36=	synonymous_variant	1/5	ENST00000007516.8	NP_004994.1
NDUFAB1	XM_011545856.3	c.108C>G	p.Leu36=	synonymous_variant	1/6		XP_011544158.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFAB1	ENST00000007516.8	c.108C>G	p.Leu36=	synonymous_variant	1/5	1	NM_005003.3	ENSP00000007516	P1
NDUFAB1	ENST00000570319.5	c.108C>G	p.Leu36=	synonymous_variant	1/4	1		ENSP00000458770	P1
NDUFAB1	ENST00000562133.5	c.96C>G	p.Leu32=	synonymous_variant	1/4	2		ENSP00000454891
NDUFAB1	ENST00000484769.1	c.108C>G	p.Leu36=	synonymous_variant, NMD_transcript_variant	1/6	3		ENSP00000454812

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16199 AN: 152184 Hom.: 1038 Cov.: 33

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.0747

Gnomad ASJ AF: 0.0438

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.0769

Gnomad FIN AF: 0.0975

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.0740

Gnomad OTH AF: 0.0989

GnomAD3 exomes AF: 0.0864 AC: 20848 AN: 241426 Hom.: 1044 AF XY: 0.0848 AC XY: 11231 AN XY: 132488

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.0651

Gnomad ASJ exome AF: 0.0398

Gnomad EAS exome AF: 0.174

Gnomad SAS exome AF: 0.0762

Gnomad FIN exome AF: 0.0978

Gnomad NFE exome AF: 0.0727

Gnomad OTH exome AF: 0.0791

GnomAD4 exome AF: 0.0793 AC: 115680 AN: 1458532 Hom.: 5227 Cov.: 32 AF XY: 0.0789 AC XY: 57275 AN XY: 725564

Gnomad4 AFR exome AF: 0.177

Gnomad4 AMR exome AF: 0.0692

Gnomad4 ASJ exome AF: 0.0397

Gnomad4 EAS exome AF: 0.190

Gnomad4 SAS exome AF: 0.0726

Gnomad4 FIN exome AF: 0.0954

Gnomad4 NFE exome AF: 0.0729

Gnomad4 OTH exome AF: 0.0922

GnomAD4 genome AF: 0.107 AC: 16243 AN: 152298 Hom.: 1049 Cov.: 33 AF XY: 0.106 AC XY: 7920 AN XY: 74468

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.0746

Gnomad4 ASJ AF: 0.0438

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.0772

Gnomad4 FIN AF: 0.0975

Gnomad4 NFE AF: 0.0740

Gnomad4 OTH AF: 0.0984

Alfa AF: 0.0780 Hom.: 183

Bravo AF: 0.109

Asia WGS AF: 0.126 AC: 436 AN: 3478

EpiCase AF: 0.0740

EpiControl AF: 0.0734

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.0
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs466719; hg19: chr16-23607504; COSMIC: COSV50287287;