11-67606685-A-T

Variant names:

• chr11-67606685-A-T
• rs2514013
• ENST00000647561.1:c.-320A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000647561.1(NDUFV1):​c.-320A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NDUFV1 ENST00000647561.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.924
• Publications: 1 publications found

Genes affected

NDUFV1 (HGNC:7716): (NADH:ubiquinone oxidoreductase core subunit V1) The mitochondrial respiratory chain provides energy to cells via oxidative phosphorylation and consists of four membrane-bound electron-transporting protein complexes (I-IV) and an ATP synthase (complex V). This gene encodes a 51 kDa subunit of the NADH:ubiquinone oxidoreductase complex I; a large complex with at least 45 nuclear and mitochondrial encoded subunits that liberates electrons from NADH and channels them to ubiquinone. This subunit carries the NADH-binding site as well as flavin mononucleotide (FMN)- and Fe-S-biding sites. Defects in complex I are a common cause of mitochondrial dysfunction; a syndrome that occurs in approximately 1 in 10,000 live births. Mitochondrial complex I deficiency is linked to myopathies, encephalomyopathies, and neurodegenerative disorders such as Parkinson's disease and Leigh syndrome. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Oct 2009]

NDUFV1-DT (HGNC:26915): (NDUFV1 divergent transcript)

ENSG00000255119 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000647561.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFV1-DT	NR_130935.1		n.22T>A		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFV1	ENST00000647561.1		c.-320A>T		5_prime_UTR	Exon 2 of 11	ENSP00000497587.1	P49821-1
	NDUFV1-DT	ENST00000333139.3	TSL:2	n.22T>A		non_coding_transcript_exon	Exon 1 of 3
	NDUFV1-DT	ENST00000810663.1		n.82T>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 302760 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 160356

African (AFR) AF: 0.00 AC: 0 AN: 8754

American (AMR) AF: 0.00 AC: 0 AN: 13902

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8996

East Asian (EAS) AF: 0.00 AC: 0 AN: 17540

South Asian (SAS) AF: 0.00 AC: 0 AN: 42226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16968

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1226

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 175972

Other (OTH) AF: 0.00 AC: 0 AN: 17176

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 154775

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.52
PhyloP100		-0.92
PromoterAI		-0.033	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2514013; hg19: chr11-67374156;