chr5-60945305-G-T

Variant names:

• chr5-60945305-G-T
• NM_174889.5:c.50G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_174889.5(NDUFAF2):​c.50G>T​(p.Arg17Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NDUFAF2 NM_174889.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.723

Genes affected

NDUFAF2 (HGNC:28086): (NADH:ubiquinone oxidoreductase complex assembly factor 2) NADH:ubiquinone oxidoreductase (complex I) catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the inner mitochondrial membrane. This gene encodes a complex I assembly factor. Mutations in this gene cause progressive encephalopathy resulting from mitochondrial complex I deficiency. [provided by RefSeq, Jul 2008]

ERCC8 (HGNC:3439): (ERCC excision repair 8, CSA ubiquitin ligase complex subunit) This gene encodes a WD repeat protein, which interacts with Cockayne syndrome type B (CSB) protein and with p44 protein, a subunit of the RNA polymerase II transcription factor IIH. Mutations in this gene have been identified in patients with hereditary disease Cockayne syndrome (CS). CS cells are abnormally sensitive to ultraviolet radiation and are defective in the repair of transcriptionally active genes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17145771).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFAF2	NM_174889.5	c.50G>T	p.Arg17Met	missense_variant	Exon 1 of 4	ENST00000296597.10	NP_777549.1
ERCC8	NM_000082.4	c.-297C>A		upstream_gene_variant		ENST00000676185.1	NP_000073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFAF2	ENST00000296597.10	c.50G>T	p.Arg17Met	missense_variant	Exon 1 of 4	1	NM_174889.5	ENSP00000296597.5
ERCC8	ENST00000676185.1	c.-297C>A		upstream_gene_variant			NM_000082.4	ENSP00000501614.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461770 Hom.: 0 Cov.: 68 AF XY: 0.00000138 AC XY: 1 AN XY: 727176

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.047	T;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.80	T
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.053
Sift	Benign	0.037	D;D
Sift4G	Uncertain	0.046	D;D
Polyphen		0.45	P;.
Vest4		0.31
MutPred		0.37		Loss of MoRF binding (P = 0.0298);Loss of MoRF binding (P = 0.0298);
MVP		0.74
MPC		0.14
ClinPred		0.36	T
GERP RS		3.0
Varity_R		0.065
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-60241132;