1-161208894-T-C

Variant names:

• chr1-161208894-T-C
• rs3924264
• NM_001377299.1:c.394-299T>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001377299.1(NDUFS2):​c.394-299T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,094 control chromosomes in the GnomAD database, including 11,561 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.39 (11561 hom., cov: 32)
• Consequence: NDUFS2 NM_001377299.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.114

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-161208894-T-C is Benign according to our data. Variant chr1-161208894-T-C is described in ClinVar as [Benign]. Clinvar id is 671138.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFS2	NM_001377299.1	c.394-299T>C		intron_variant	Intron 3 of 13	ENST00000676972.1	NP_001364228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFS2	ENST00000676972.1	c.394-299T>C		intron_variant	Intron 3 of 13		NM_001377299.1	ENSP00000503117.1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58771 AN: 151976 Hom.: 11544 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.387 AC: 58832 AN: 152094 Hom.: 11561 Cov.: 32 AF XY: 0.390 AC XY: 28996 AN XY: 74346

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.401

Alfa AF: 0.364 Hom.: 10553

Bravo AF: 0.393

Asia WGS AF: 0.473 AC: 1643 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.75

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: rs3924264; hg19: chr1-161178684;