2-37232165-C-G

Position:

• chr2-37232165-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144736.5(NDUFAF7):​c.115C>G​(p.Pro39Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,614,094 control chromosomes in the GnomAD database, including 2,072 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.066 (1063 hom., cov: 33)
  • Exomes 𝑓: 0.0066 (1009 hom.)
• Consequence: NDUFAF7 NM_144736.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.315

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019940436).
• BP6: Variant 2-37232165-C-G is Benign according to our data. Variant chr2-37232165-C-G is described in ClinVar as [Benign]. Clinvar id is 138462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFAF7	NM_144736.5	c.115C>G	p.Pro39Ala	missense_variant	2/10	ENST00000002125.9	NP_653337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFAF7	ENST00000002125.9	c.115C>G	p.Pro39Ala	missense_variant	2/10	1	NM_144736.5	ENSP00000002125.4

Frequencies

GnomAD3 genomes AF: 0.0655 AC: 9956 AN: 152114 Hom.: 1061 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0279

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0464

GnomAD3 exomes AF: 0.0172 AC: 4328 AN: 251486 Hom.: 449 AF XY: 0.0123 AC XY: 1665 AN XY: 135918

Gnomad AFR exome AF: 0.233

Gnomad AMR exome AF: 0.0112

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000392

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000765

Gnomad OTH exome AF: 0.00831

GnomAD4 exome AF: 0.00662 AC: 9674 AN: 1461862 Hom.: 1009 Cov.: 33 AF XY: 0.00558 AC XY: 4060 AN XY: 727234

Gnomad4 AFR exome AF: 0.230

Gnomad4 AMR exome AF: 0.0125

Gnomad4 ASJ exome AF: 0.000842

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000441

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000371

Gnomad4 OTH exome AF: 0.0147

GnomAD4 genome AF: 0.0655 AC: 9975 AN: 152232 Hom.: 1063 Cov.: 33 AF XY: 0.0624 AC XY: 4649 AN XY: 74452

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.0279

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000691

Gnomad4 OTH AF: 0.0459

Alfa AF: 0.00421 Hom.: 33

Bravo AF: 0.0747

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.223 AC: 982

ESP6500EA AF: 0.00163 AC: 14

ExAC AF: 0.0209 AC: 2534

Asia WGS AF: 0.0120 AC: 41 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 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	0.061
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.80
DEOGEN2	Benign	0.0020	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.46	T;T
MetaRNN	Benign	0.0020	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.65	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.080	N;N
REVEL	Benign	0.027
Sift	Benign	0.71	T;T
Sift4G	Benign	0.75	T;T
Polyphen		0.0	B;B
Vest4		0.064
MPC		0.024
ClinPred		0.00052	T
GERP RS		2.7
Varity_R		0.025
gMVP		0.44

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

Other links and lift over

dbSNP: rs2714473; hg19: chr2-37459308;