16-23587199-T-C

Position:

• chr16-23587199-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000007516.8(NDUFAB1):​c.289A>G​(p.Lys97Glu) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NDUFAB1 ENST00000007516.8 missense, splice_region
• Scores: Splicing: ADA: 0.08840
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.64

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFAB1	NM_005003.3	c.289A>G	p.Lys97Glu	missense_variant, splice_region_variant	2/5	ENST00000007516.8	NP_004994.1
NDUFAB1	XM_011545856.3	c.382A>G	p.Lys128Glu	missense_variant, splice_region_variant	3/6		XP_011544158.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFAB1	ENST00000007516.8	c.289A>G	p.Lys97Glu	missense_variant, splice_region_variant	2/5	1	NM_005003.3	ENSP00000007516	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2022

The c.289A>G (p.K97E) alteration is located in exon 2 (coding exon 2) of the NDUFAB1 gene. This alteration results from a A to G substitution at nucleotide position 289, causing the lysine (K) at amino acid position 97 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;T;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	.;D;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.4	L;L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.5	D;.;.
REVEL	Benign	0.25
Sift	Uncertain	0.0020	D;.;.
Sift4G	Uncertain	0.0030	D;D;T
Polyphen		0.98	D;D;.
Vest4		0.64
MutPred		0.35		Loss of ubiquitination at K97 (P = 0.0116);Loss of ubiquitination at K97 (P = 0.0116);.;
MVP		0.57
MPC		1.1
ClinPred		0.96	D
GERP RS		4.6
Varity_R		0.92
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.088
dbscSNV1_RF	Benign	0.40
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-23598520;