rs1053517

chr2-206122291-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005006.7(NDUFS1):c.*1894T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 151,580 control chromosomes in the GnomAD database, including 22,388 homozygotes. 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: 𝑓 0.52 (22387 hom., cov: 29)
  • Exomes 𝑓: 0.36 (1 hom.)
• Consequence: NDUFS1 NM_005006.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFS1	NM_005006.7	c.*1894T>C		3_prime_UTR_variant	19/19	ENST00000233190.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFS1	ENST00000233190.11	c.*1894T>C		3_prime_UTR_variant	19/19	1	NM_005006.7	P1
	ENST00000453039.1	n.1379A>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79283 AN: 151448 Hom.: 22345 Cov.: 29

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.531

GnomAD4 exome AF: 0.357 AC: 5 AN: 14 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 3 AN XY: 6

Gnomad4 NFE exome AF: 0.417

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.524 AC: 79378 AN: 151566 Hom.: 22387 Cov.: 29 AF XY: 0.522 AC XY: 38654 AN XY: 74006

Gnomad4 AFR AF: 0.736

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.526

Alfa AF: 0.452 Hom.: 20782

Bravo AF: 0.533

Asia WGS AF: 0.320 AC: 1115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.0
Dann	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1053517; hg19: chr2-206987015;