Variant chr19-14566152-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004146.6(NDUFB7):c.395A>G(p.Asp132Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,459,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

NDUFB7
NM_004146.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.67

Variant links:

Genes affected

NDUFB7 (HGNC:7702): (NADH:ubiquinone oxidoreductase subunit B7) 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 is located 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. [provided by RefSeq, Jul 2008]

NDUFB7 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.023742408).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFB7	NM_004146.6 link	c.395A>G	p.Asp132Gly	missense_variant	3/3	ENST00000215565.3	NP_004137.2	P17568
NDUFB7	XM_011528039.4 link	c.281A>G	p.Asp94Gly	missense_variant	3/3		XP_011526341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NDUFB7	ENST00000215565.3 link	c.395A>G	p.Asp132Gly	missense_variant	3/3	1	NM_004146.6	ENSP00000215565.1	P17568
NDUFB7	ENST00000593353.5 link	n.*180A>G		non_coding_transcript_exon_variant	3/3	2		ENSP00000473120.1	M0R3B8
NDUFB7	ENST00000593353.5 link	n.*180A>G		3_prime_UTR_variant	3/3	2		ENSP00000473120.1	M0R3B8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1459996

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726216

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000360

Gnomad4 OTH exome

AF:

0.0000664

GnomAD4 genome

Cov.:

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

Oct 01, 2024

The c.395A>G (p.D132G) alteration is located in exon 3 (coding exon 3) of the NDUFB7 gene. This alteration results from a A to G substitution at nucleotide position 395, causing the aspartic acid (D) at amino acid position 132 to be replaced by a glycine (G). 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

0.085

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.40

DANN

Benign

0.59

DEOGEN2

Benign

0.081

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.47

M_CAP

Benign

0.0035

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.20

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.35

REVEL

Benign

0.031

Sift

Benign

0.82

Sift4G

Benign

0.75

Polyphen

0.0

Vest4

0.032

MutPred

0.10

Gain of MoRF binding (P = 0.0323);

MVP

0.12

MPC

0.19

ClinPred

0.028

GERP RS

-4.6

Varity_R

0.029

gMVP

0.50

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over