16-23596192-G-T

Position:

• chr16-23596192-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005003.3(NDUFAB1):​c.99C>A​(p.Ser33Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NDUFAB1 NM_005003.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.13

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2294519).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFAB1	NM_005003.3	c.99C>A	p.Ser33Arg	missense_variant	1/5	ENST00000007516.8	NP_004994.1
NDUFAB1	XM_011545856.3	c.99C>A	p.Ser33Arg	missense_variant	1/6		XP_011544158.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFAB1	ENST00000007516.8	c.99C>A	p.Ser33Arg	missense_variant	1/5	1	NM_005003.3	ENSP00000007516	P1
NDUFAB1	ENST00000570319.5	c.99C>A	p.Ser33Arg	missense_variant	1/4	1		ENSP00000458770	P1
NDUFAB1	ENST00000562133.5	c.87C>A	p.Ser29Arg	missense_variant	1/4	2		ENSP00000454891
NDUFAB1	ENST00000484769.1	c.99C>A	p.Ser33Arg	missense_variant, NMD_transcript_variant	1/6	3		ENSP00000454812

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Feb 06, 2024

The c.99C>A (p.S33R) alteration is located in exon 1 (coding exon 1) of the NDUFAB1 gene. This alteration results from a C to A substitution at nucleotide position 99, causing the serine (S) at amino acid position 33 to be replaced by an arginine (R). 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	Benign	0.28
BayesDel_addAF	Benign	-0.0058	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.71	.;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.3	N;.
REVEL	Benign	0.065
Sift	Benign	0.074	T;.
Sift4G	Benign	0.30	T;T
Polyphen		0.10	B;B
Vest4		0.27
MutPred		0.44		Gain of MoRF binding (P = 0.0123);Gain of MoRF binding (P = 0.0123);
MVP		0.37
MPC		0.31
ClinPred		0.67	D
GERP RS		3.3
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.19
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-23607513;