chr2-37231669-AG-A

Position:

• chr2-37231669-AG-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_144736.5(NDUFAF7):​c.-36delG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000916 in 1,520,728 control chromosomes in the GnomAD database, including 21 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00089 (18 hom.)
• Consequence: NDUFAF7 NM_144736.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.163

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 2-37231669-AG-A is Benign according to our data. Variant chr2-37231669-AG-A is described in ClinVar as [Benign]. Clinvar id is 418379.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFAF7	NM_144736.5	c.-36delG		5_prime_UTR_variant	1/10	ENST00000002125.9	NP_653337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFAF7	ENST00000002125	c.-36delG		5_prime_UTR_variant	1/10	1	NM_144736.5	ENSP00000002125.4

Frequencies

GnomAD3 genomes AF: 0.00117 AC: 171 AN: 145726 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00150

Gnomad ASJ AF: 0.0401

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000671

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000782

Gnomad OTH AF: 0.00256

GnomAD3 exomes AF: 0.00160 AC: 403 AN: 251118 Hom.: 4 AF XY: 0.00149 AC XY: 202 AN XY: 135844

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.0330

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000555

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000291

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.000889 AC: 1222 AN: 1375002 Hom.: 18 Cov.: 34 AF XY: 0.000895 AC XY: 612 AN XY: 683870

Gnomad4 AFR exome AF: 0.0000605

Gnomad4 AMR exome AF: 0.000347

Gnomad4 ASJ exome AF: 0.0349

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000686

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000159

Gnomad4 OTH exome AF: 0.00231

GnomAD4 genome AF: 0.00117 AC: 171 AN: 145726 Hom.: 3 Cov.: 33 AF XY: 0.00112 AC XY: 80 AN XY: 71134

Gnomad4 AFR AF: 0.000122

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.0401

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000671

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000782

Gnomad4 OTH AF: 0.00256

Bravo AF: 0.00119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 20, 2016

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

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: rs769474358; hg19: chr2-37458812;