Variant chr2-37231728-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_144736.5(NDUFAF7):c.23G>A(p.Gly8Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000289 in 1,614,216 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

NDUFAF7
NM_144736.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.85

Variant links:

Genes affected

NDUFAF7 (HGNC:28816): (NADH:ubiquinone oxidoreductase complex assembly factor 7) This gene encodes an assembly factor protein which helps in the assembly and stabilization of Complex I, a large multi-subunit enzyme in the mitochondrial respiratory chain. Complex I is involved in several physiological activities in the cell, including metabolite transport and ATP synthesis. The encoded protein is a methyltransferase which methylates Arg85 of a subunit of Complex I in the early stages of its assembly. A pseudogene related to this gene is located on chromosome 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

NDUFAF7 links:

NDUFAF7 (HGNC:):

NDUFAF7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004567176).

BP6

Variant 2-37231728-G-A is Benign according to our data. Variant chr2-37231728-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 214761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFAF7	NM_144736.5 linkuse as main transcript	c.23G>A	p.Gly8Asp	missense_variant	1/10	ENST00000002125.9	NP_653337.1	Q7L592-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFAF7	ENST00000002125.9 linkuse as main transcript	c.23G>A	p.Gly8Asp	missense_variant	1/10	1	NM_144736.5	ENSP00000002125.4		Q7L592-1

Frequencies

GnomAD3 genomes

AF:

0.00160

AC:

243

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000438

AC:

110

AN:

251180

Hom.:

AF XY:

0.000390

AC XY:

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.00628

Gnomad AMR exome

AF:

0.000202

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:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000153

AC:

223

AN:

1461878

Hom.:

Cov.:

AF XY:

0.000133

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00565

Gnomad4 AMR exome

AF:

0.000313

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:

0.000265

GnomAD4 genome

AF:

0.00160

AC:

243

AN:

152338

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

111

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00553

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000269

Hom.:

Bravo

AF:

0.00193

ESP6500AA

AF:

0.00658

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000486

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 24, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 30, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0041

T;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.75

N;N

REVEL

Benign

0.17

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.017

D;D

Polyphen

0.61

P;P

Vest4

0.47

MVP

0.11

MPC

0.058

ClinPred

0.096

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.15

gMVP

0.45

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