rs147787116

Positions:

• chr11-67612107-GC-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_007103.4(NDUFV1):​c.1163-12del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,613,708 control chromosomes in the GnomAD database, including 36 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0093 (20 hom., cov: 32)
  • Exomes 𝑓: 0.00086 (16 hom.)
• Consequence: NDUFV1 NM_007103.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.10

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 11-67612107-GC-G is Benign according to our data. Variant chr11-67612107-GC-G is described in ClinVar as [Likely_benign]. Clinvar id is 214844.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00929 (1411/151920) while in subpopulation AFR AF= 0.0323 (1339/41402). AF 95% confidence interval is 0.0309. There are 20 homozygotes in gnomad4. There are 659 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFV1	NM_007103.4	c.1163-12del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000322776.11	NP_009034.2
NDUFV1	NM_001166102.2	c.1136-12del		splice_polypyrimidine_tract_variant, intron_variant			NP_001159574.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFV1	ENST00000322776.11	c.1163-12del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_007103.4	ENSP00000322450	P1

Frequencies

GnomAD3 genomes AF: 0.00928 AC: 1409 AN: 151802 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.0324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00361

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00256 AC: 643 AN: 251210 Hom.: 9 AF XY: 0.00198 AC XY: 269 AN XY: 135812

Gnomad AFR exome AF: 0.0351

Gnomad AMR exome AF: 0.00179

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000863 AC: 1261 AN: 1461788 Hom.: 16 Cov.: 32 AF XY: 0.000716 AC XY: 521 AN XY: 727190

Gnomad4 AFR exome AF: 0.0306

Gnomad4 AMR exome AF: 0.00195

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000324

Gnomad4 OTH exome AF: 0.00179

GnomAD4 genome AF: 0.00929 AC: 1411 AN: 151920 Hom.: 20 Cov.: 32 AF XY: 0.00888 AC XY: 659 AN XY: 74250

Gnomad4 AFR AF: 0.0323

Gnomad4 AMR AF: 0.00360

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.000524 Hom.: 0

Bravo AF: 0.0106

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Sep 04, 2015	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 28, 2012

The variant is found in MITONUC-MITOP panel(s). -

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: rs147787116; hg19: chr11-67379578;