2-37232210-A-G

Position:

• chr2-37232210-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144736.5(NDUFAF7):​c.160A>G​(p.Thr54Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: NDUFAF7 NM_144736.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.03

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38515484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFAF7	NM_144736.5	c.160A>G	p.Thr54Ala	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.160A>G	p.Thr54Ala	missense_variant	2/10	1	NM_144736.5	ENSP00000002125.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251490 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135920

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461636 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727108

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000312 Hom.: 0

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;.;.;.;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.93	D;D;D;D;D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.39	T;T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.1	M;M;.;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.1	D;D;D;D;D
REVEL	Uncertain	0.34
Sift	Benign	0.040	D;T;T;T;T
Sift4G	Benign	0.10	T;T;T;T;T
Polyphen		0.79	P;P;.;.;.
Vest4		0.18
MutPred		0.38		Gain of MoRF binding (P = 0.1152);Gain of MoRF binding (P = 0.1152);.;.;.;
MVP		0.56
MPC		0.028
ClinPred		0.82	D
GERP RS		4.5
Varity_R		0.18
gMVP		0.69

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: rs1195059937; hg19: chr2-37459353;