Variant 2-37231670-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_144736.5(NDUFAF7):c.-36G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 1,611,546 control chromosomes in the GnomAD database, including 817 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 48 hom., cov: 33)

Exomes 𝑓: 0.030 ( 769 hom. )

Consequence

NDUFAF7
NM_144736.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.163

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 (BayesDel_noAF=-0.81).

BP6

Variant 2-37231670-G-C is Benign according to our data. Variant chr2-37231670-G-C is described in ClinVar as [Benign]. Clinvar id is 138466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0216 (3286/152016) while in subpopulation SAS AF= 0.04 (193/4826). AF 95% confidence interval is 0.0354. There are 48 homozygotes in gnomad4. There are 1643 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFAF7	NM_144736.5 linkuse as main transcript	c.-36G>C		5_prime_UTR_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 linkuse as main transcript	c.-36G>C		5_prime_UTR_variant	1/10	1	NM_144736.5	ENSP00000002125.4		Q7L592-1

Frequencies

GnomAD3 genomes

AF:

0.0216

AC:

3282

AN:

151898

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00601

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0199

Gnomad ASJ

AF:

0.0347

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0393

Gnomad FIN

AF:

0.0245

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0306

Gnomad OTH

AF:

0.0337

GnomAD3 exomes

AF:

0.0255

AC:

6404

AN:

251132

Hom.:

125

AF XY:

0.0266

AC XY:

3610

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.00567

Gnomad AMR exome

AF:

0.0154

Gnomad ASJ exome

AF:

0.0350

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0344

Gnomad FIN exome

AF:

0.0268

Gnomad NFE exome

AF:

0.0317

Gnomad OTH exome

AF:

0.0317

GnomAD4 exome

AF:

0.0303

AC:

44249

AN:

1459530

Hom.:

769

Cov.:

AF XY:

0.0304

AC XY:

22096

AN XY:

726066

show subpopulations

Gnomad4 AFR exome

AF:

0.00636

Gnomad4 AMR exome

AF:

0.0167

Gnomad4 ASJ exome

AF:

0.0363

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0363

Gnomad4 FIN exome

AF:

0.0288

Gnomad4 NFE exome

AF:

0.0320

Gnomad4 OTH exome

AF:

0.0322

GnomAD4 genome

AF:

0.0216

AC:

3286

AN:

152016

Hom.:

Cov.:

AF XY:

0.0221

AC XY:

1643

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00601

Gnomad4 AMR

AF:

0.0198

Gnomad4 ASJ

AF:

0.0347

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0400

Gnomad4 FIN

AF:

0.0245

Gnomad4 NFE

AF:

0.0306

Gnomad4 OTH

AF:

0.0333

Alfa

AF:

0.00794

Hom.:

Bravo

AF:

0.0205

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 19, 2013

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.3

DANN

Benign

0.42

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