11-67606525-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000533876.1(ENSG00000255119):n.439dup variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 228,450 control chromosomes in the GnomAD database, including 26 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (12 hom., cov: 31)
  • Exomes 𝑓: 0.012 (14 hom.)
• Consequence: ENST00000533876.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.285

Genes affected

(HGNC:):

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

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-67606525-C-CT is Benign according to our data. Variant chr11-67606525-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 1195099.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0113 (1717/152202) while in subpopulation NFE AF= 0.0174 (1184/67998). AF 95% confidence interval is 0.0166. There are 12 homozygotes in gnomad4. There are 790 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFV1-DT	NR_130935.1	n.88+93_88+94insA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000533876.1	n.439dup		non_coding_transcript_exon_variant	2/2	4
NDUFV1-DT	ENST00000333139.3	n.88+93_88+94insA		intron_variant, non_coding_transcript_variant		2
NDUFV1	ENST00000647561.1	c.-479dup		5_prime_UTR_variant	2/11			P1

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1718 AN: 152084 Hom.: 12 Cov.: 31

Gnomad AFR AF: 0.00278

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00725

Gnomad FIN AF: 0.00905

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0174

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.0120 AC: 912 AN: 76248 Hom.: 14 Cov.: 0 AF XY: 0.0114 AC XY: 463 AN XY: 40678

Gnomad4 AFR exome AF: 0.00183

Gnomad4 AMR exome AF: 0.00996

Gnomad4 ASJ exome AF: 0.00632

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00881

Gnomad4 FIN exome AF: 0.00734

Gnomad4 NFE exome AF: 0.0149

Gnomad4 OTH exome AF: 0.0133

GnomAD4 genome AF: 0.0113 AC: 1717 AN: 152202 Hom.: 12 Cov.: 31 AF XY: 0.0106 AC XY: 790 AN XY: 74414

Gnomad4 AFR AF: 0.00277

Gnomad4 AMR AF: 0.0101

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00726

Gnomad4 FIN AF: 0.00905

Gnomad4 NFE AF: 0.0174

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.0122 Hom.: 3

Bravo AF: 0.0116

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs200876962; hg19: chr11-67373996;