2-37232040-C-T

Position:

• chr2-37232040-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_144736.5(NDUFAF7):​c.56-66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 1,612,622 control chromosomes in the GnomAD database, including 3,316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.083 (1736 hom., cov: 33)
  • Exomes 𝑓: 0.0084 (1580 hom.)
• Consequence: NDUFAF7 NM_144736.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.663

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-37232040-C-T is Benign according to our data. Variant chr2-37232040-C-T is described in ClinVar as [Benign]. Clinvar id is 1268049.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFAF7	NM_144736.5	c.56-66C>T		intron_variant		ENST00000002125.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFAF7	ENST00000002125.9	c.56-66C>T		intron_variant		1	NM_144736.5	P1

Frequencies

GnomAD3 genomes AF: 0.0828 AC: 12599 AN: 152148 Hom.: 1734 Cov.: 33

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0340

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000911

Gnomad OTH AF: 0.0612

GnomAD4 exome AF: 0.00837 AC: 12227 AN: 1460356 Hom.: 1580 Cov.: 32 AF XY: 0.00706 AC XY: 5132 AN XY: 726550

Gnomad4 AFR exome AF: 0.294

Gnomad4 AMR exome AF: 0.0153

Gnomad4 ASJ exome AF: 0.000842

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000499

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000443

Gnomad4 OTH exome AF: 0.0183

GnomAD4 genome AF: 0.0829 AC: 12623 AN: 152266 Hom.: 1736 Cov.: 33 AF XY: 0.0788 AC XY: 5865 AN XY: 74460

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.0340

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000911

Gnomad4 OTH AF: 0.0605

Alfa AF: 0.0976 Hom.: 231

Bravo AF: 0.0952

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.86

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: rs2430496; hg19: chr2-37459183;