2-206123338-TA-T

Position:

• chr2-206123338-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000233190.11(NDUFS1):​c.*846del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0762 in 132,732 control chromosomes in the GnomAD database, including 479 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.076 (479 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: NDUFS1 ENST00000233190.11 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.106

Genes affected

NDUFS1 (HGNC:7707): (NADH:ubiquinone oxidoreductase core subunit S1) The protein encoded by this gene belongs to the complex I 75 kDa subunit family. Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. This protein is the largest subunit of complex I and it is a component of the iron-sulfur (IP) fragment of the enzyme. It may form part of the active site crevice where NADH is oxidized. Mutations in this gene are associated with complex I deficiency. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-206123338-TA-T is Benign according to our data. Variant chr2-206123338-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 333765.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFS1	NM_005006.7	c.*846del		3_prime_UTR_variant	19/19	ENST00000233190.11	NP_004997.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFS1	ENST00000233190.11	c.*846del		3_prime_UTR_variant	19/19	1	NM_005006.7	ENSP00000233190	P1

Frequencies

GnomAD3 genomes AF: 0.0762 AC: 10107 AN: 132694 Hom.: 479 Cov.: 30

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.0265

Gnomad AMR AF: 0.0425

Gnomad ASJ AF: 0.0428

Gnomad EAS AF: 0.0572

Gnomad SAS AF: 0.0702

Gnomad FIN AF: 0.0877

Gnomad MID AF: 0.0417

Gnomad NFE AF: 0.0376

Gnomad OTH AF: 0.0700

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0762 AC: 10113 AN: 132732 Hom.: 479 Cov.: 30 AF XY: 0.0774 AC XY: 4950 AN XY: 63984

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.0423

Gnomad4 ASJ AF: 0.0428

Gnomad4 EAS AF: 0.0570

Gnomad4 SAS AF: 0.0699

Gnomad4 FIN AF: 0.0877

Gnomad4 NFE AF: 0.0376

Gnomad4 OTH AF: 0.0689

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Mitochondrial complex I deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Leigh syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs58253838; hg19: chr2-206988062;