NM_144736.5:c.217-1453C>T

Variant names:

• chr2-37234643-C-T
• rs6743961
• NM_144736.5:c.217-1453C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144736.5(NDUFAF7):​c.217-1453C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 151,906 control chromosomes in the GnomAD database, including 18,978 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (18978 hom., cov: 31)
• Consequence: NDUFAF7 NM_144736.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFAF7	NM_144736.5	c.217-1453C>T		intron_variant	Intron 2 of 9	ENST00000002125.9	NP_653337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFAF7	ENST00000002125.9	c.217-1453C>T		intron_variant	Intron 2 of 9	1	NM_144736.5	ENSP00000002125.4

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74374 AN: 151786 Hom.: 18966 Cov.: 31

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.532

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.490 AC: 74433 AN: 151906 Hom.: 18978 Cov.: 31 AF XY: 0.499 AC XY: 37057 AN XY: 74246

African (AFR) AF: 0.383 AC: 15842 AN: 41410

American (AMR) AF: 0.577 AC: 8819 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2088 AN: 3468

East Asian (EAS) AF: 0.780 AC: 4024 AN: 5158

South Asian (SAS) AF: 0.395 AC: 1904 AN: 4816

European-Finnish (FIN) AF: 0.620 AC: 6534 AN: 10532

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.493 AC: 33506 AN: 67932

Other (OTH) AF: 0.538 AC: 1136 AN: 2112

Alfa AF: 0.505 Hom.: 24315

Bravo AF: 0.491

Asia WGS AF: 0.589 AC: 2045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.26
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6743961; hg19: chr2-37461786;