rs3924264

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-161208894-T-C
• chr1-161208894-T-A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 publications found

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]

NDUFS2 Gene-Disease associations (from GenCC):

• Leigh syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial complex I deficiency, nuclear type 6

  Inheritance: Unknown, AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Leigh syndrome with cardiomyopathy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome with leukodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial complex I deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leber hereditary optic neuropathy

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377299.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFS2	NM_001377299.1	MANE Select	c.394-299T>C		intron	N/A	NP_001364228.1	O75306-1
	NDUFS2	NM_001377298.1		c.394-299T>C		intron	N/A	NP_001364227.1	O75306-1
	NDUFS2	NM_004550.5		c.394-299T>C		intron	N/A	NP_004541.1	O75306-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFS2	ENST00000676972.1	MANE Select	c.394-299T>C		intron	N/A	ENSP00000503117.1	O75306-1
	NDUFS2	ENST00000367993.7	TSL:1	c.394-299T>C		intron	N/A	ENSP00000356972.3	O75306-1
	NDUFS2	ENST00000392179.5	TSL:1	c.394-299T>C		intron	N/A	ENSP00000376018.4	O75306-2

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

African (AFR) AF: 0.414 AC: 17150 AN: 41472

American (AMR) AF: 0.387 AC: 5921 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1218 AN: 3468

East Asian (EAS) AF: 0.491 AC: 2544 AN: 5186

South Asian (SAS) AF: 0.484 AC: 2334 AN: 4824

European-Finnish (FIN) AF: 0.400 AC: 4217 AN: 10552

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24205 AN: 67980

Other (OTH) AF: 0.401 AC: 847 AN: 2114

Alfa AF: 0.370 Hom.: 15635

Bravo AF: 0.393

Asia WGS AF: 0.473 AC: 1643 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.75
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3924264; hg19: chr1-161178684;