16-23596183-G-C

Variant names:

• chr16-23596183-G-C
• rs466719
• NM_005003.3:c.108C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005003.3(NDUFAB1):​c.108C>G​(p.Leu36Leu) 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
• Publications: 10 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005003.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFAB1	NM_005003.3	MANE Select	c.108C>G	p.Leu36Leu	synonymous	Exon 1 of 5	NP_004994.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFAB1	ENST00000007516.8	TSL:1 MANE Select	c.108C>G	p.Leu36Leu	synonymous	Exon 1 of 5	ENSP00000007516.2
	NDUFAB1	ENST00000570319.5	TSL:1	c.108C>G	p.Leu36Leu	synonymous	Exon 1 of 4	ENSP00000458770.1
	NDUFAB1	ENST00000562133.5	TSL:2	c.93C>G	p.Leu31Leu	synonymous	Exon 1 of 4	ENSP00000454891.1

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

GnomAD2 exomes AF: 0.0864 AC: 20848 AN: 241426 AF XY: 0.0848

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 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

African (AFR) AF: 0.177 AC: 5861 AN: 33040

American (AMR) AF: 0.0692 AC: 3085 AN: 44572

Ashkenazi Jewish (ASJ) AF: 0.0397 AC: 1033 AN: 26038

East Asian (EAS) AF: 0.190 AC: 7512 AN: 39464

South Asian (SAS) AF: 0.0726 AC: 6245 AN: 86004

European-Finnish (FIN) AF: 0.0954 AC: 5008 AN: 52500

Middle Eastern (MID) AF: 0.0679 AC: 391 AN: 5758

European-Non Finnish (NFE) AF: 0.0729 AC: 80989 AN: 1110924

Other (OTH) AF: 0.0922 AC: 5556 AN: 60232

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

African (AFR) AF: 0.177 AC: 7358 AN: 41568

American (AMR) AF: 0.0746 AC: 1142 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0438 AC: 152 AN: 3472

East Asian (EAS) AF: 0.172 AC: 887 AN: 5160

South Asian (SAS) AF: 0.0772 AC: 373 AN: 4832

European-Finnish (FIN) AF: 0.0975 AC: 1036 AN: 10626

Middle Eastern (MID) AF: 0.0753 AC: 22 AN: 292

European-Non Finnish (NFE) AF: 0.0740 AC: 5035 AN: 68014

Other (OTH) AF: 0.0984 AC: 208 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.0
DANN	Benign	0.60
PhyloP100		-0.44
PromoterAI		-0.0034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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