rs3813624

Positions:

• chr1-161201187-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000367993.7(NDUFS2):​c.-239-960C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,260 control chromosomes in the GnomAD database, including 1,451 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 0.12 (1451 hom., cov: 32)
• Consequence: NDUFS2 ENST00000367993.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148

Genes affected

NDUFS2 (HGNC:7708): (NADH:ubiquinone oxidoreductase core subunit S2) The protein encoded by this gene is a core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I). Mammalian mitochondrial complex I is composed of at least 43 different subunits, 7 of which are encoded by the mitochondrial genome, and the rest are the products of nuclear genes. The iron-sulfur protein fraction of complex I is made up of 7 subunits, including this gene product. Complex I catalyzes the NADH oxidation with concomitant ubiquinone reduction and proton ejection out of the mitochondria. Mutations in this gene are associated with mitochondrial complex I deficiency. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFS2	NM_001377298.1	c.-239-960C>T		intron_variant			NP_001364227.1
NDUFS2	NM_001377300.1	c.-239-960C>T		intron_variant			NP_001364229.1
NDUFS2	NM_001377301.1	c.-239-960C>T		intron_variant			NP_001364230.1
NDUFS2	NM_004550.5	c.-239-960C>T		intron_variant			NP_004541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFS2	ENST00000367993.7	c.-239-960C>T		intron_variant		1		ENSP00000356972	P1
NDUFS2	ENST00000676600.1	c.-76-1123C>T		intron_variant				ENSP00000503989	P1
NDUFS2	ENST00000677231.1	c.-239-960C>T		intron_variant				ENSP00000503378

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18653 AN: 152142 Hom.: 1455 Cov.: 32

Gnomad AFR AF: 0.0481

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.0985

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.128

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.122 AC: 18648 AN: 152260 Hom.: 1451 Cov.: 32 AF XY: 0.123 AC XY: 9186 AN XY: 74434

Gnomad4 AFR AF: 0.0482

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.0969

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.129

Alfa AF: 0.135 Hom.: 275

Bravo AF: 0.129

Asia WGS AF: 0.203 AC: 704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Benign	0.70

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: rs3813624; hg19: chr1-161170977;