Variant chr9-32572933-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002493.5(NDUFB6):c.128T>C(p.Met43Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,455,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NDUFB6
NM_002493.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.10

Variant links:

Genes affected

NDUFB6 (HGNC:7701): (NADH:ubiquinone oxidoreductase subunit B6) The protein encoded by this gene is a subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I). Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Alternative splicing occurs at this locus and three transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Jan 2011]

NDUFB6 links:

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ACMG classification

Classification made for transcript

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=0.21914542).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFB6	NM_002493.5 linkuse as main transcript	c.128T>C	p.Met43Thr	missense_variant	1/4	ENST00000379847.8	NP_002484.1	O95139-1
NDUFB6	NM_182739.3 linkuse as main transcript	c.128T>C	p.Met43Thr	missense_variant	1/3		NP_877416.1	O95139-2
NDUFB6	NM_001199987.2 linkuse as main transcript	c.128T>C	p.Met43Thr	missense_variant	1/3		NP_001186916.1	A0A087WZX2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NDUFB6	ENST00000379847.8 linkuse as main transcript	c.128T>C	p.Met43Thr	missense_variant	1/4	1	NM_002493.5	ENSP00000369176.3	O95139-1
NDUFB6	ENST00000350021.2 linkuse as main transcript	c.128T>C	p.Met43Thr	missense_variant	1/3	2		ENSP00000297983.3	O95139-2
NDUFB6	ENST00000366466.5 linkuse as main transcript	c.128T>C	p.Met43Thr	missense_variant	1/3	2		ENSP00000482941.1	A0A087WZX2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000408

AC:

AN:

245106

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132834

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000900

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1455746

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724376

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000313

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2024

The c.128T>C (p.M43T) alteration is located in exon 1 (coding exon 1) of the NDUFB6 gene. This alteration results from a T to C substitution at nucleotide position 128, causing the methionine (M) at amino acid position 43 to be replaced by a threonine (T). 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

0.15

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.23

T;.;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.7

L;.;L

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.6

N;.;N

REVEL

Benign

0.10

Sift

Benign

0.063

T;.;D

Sift4G

Benign

0.19

T;T;T

Polyphen

0.42

B;.;.

Vest4

0.30

MutPred

0.47

Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);

MVP

0.41

MPC

0.11

ClinPred

0.65

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.37

gMVP

0.76

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over