2-37231755-G-A

Position:

chr2-37231755-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_144736.5(NDUFAF7):c.50G>A(p.Arg17His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00797 in 1,614,172 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 42 hom., cov: 33)

Exomes 𝑓: 0.0071 ( 70 hom. )

Consequence

NDUFAF7
NM_144736.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 1.10

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030526817).

BP6

Variant 2-37231755-G-A is Benign according to our data. Variant chr2-37231755-G-A is described in ClinVar as [Benign]. Clinvar id is 138467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-37231755-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0165 (2514/152318) while in subpopulation AFR AF= 0.0431 (1792/41572). AF 95% confidence interval is 0.0414. There are 42 homozygotes in gnomad4. There are 1115 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFAF7	NM_144736.5 linkuse as main transcript	c.50G>A	p.Arg17His	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.50G>A	p.Arg17His	missense_variant	1/10	1	NM_144736.5	ENSP00000002125.4		Q7L592-1

Frequencies

GnomAD3 genomes

AF:

0.0165

AC:

2512

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0431

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0114

Gnomad ASJ

AF:

0.00836

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00688

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.00758

AC:

1903

AN:

250910

Hom.:

AF XY:

0.00665

AC XY:

903

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.0426

Gnomad AMR exome

AF:

0.00703

Gnomad ASJ exome

AF:

0.0117

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000784

Gnomad FIN exome

AF:

0.000510

Gnomad NFE exome

AF:

0.00669

Gnomad OTH exome

AF:

0.00947

GnomAD4 exome

AF:

0.00708

AC:

10344

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00677

AC XY:

4923

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0405

Gnomad4 AMR exome

AF:

0.00825

Gnomad4 ASJ exome

AF:

0.0100

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000696

Gnomad4 FIN exome

AF:

0.000917

Gnomad4 NFE exome

AF:

0.00685

Gnomad4 OTH exome

AF:

0.00921

GnomAD4 genome

AF:

0.0165

AC:

2514

AN:

152318

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

1115

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0431

Gnomad4 AMR

AF:

0.0114

Gnomad4 ASJ

AF:

0.00836

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00687

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0115

Hom.:

Bravo

AF:

0.0182

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.0422

AC:

186

ESP6500EA

AF:

0.00663

AC:

ExAC

AF:

0.00809

AC:

982

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.00758

EpiControl

AF:

0.00877

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpretted as Likely benign and reported on 10/30/2014 by GTR ID 320384. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 04, 2014

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

T;.

Eigen

Benign

-0.022

Eigen_PC

Benign

-0.038

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.81

T;T

MetaRNN

Benign

0.0031

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.092

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.020

D;D

Polyphen

0.022

B;D

Vest4

0.52

MVP

0.18

MPC

0.056

ClinPred

0.037

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.12

gMVP

0.53

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