rs13156337

Positions:

• chr5-53568965-T-C

Variant summary

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

The NM_002495.4(NDUFS4):​c.98+8205T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0757 in 152,278 control chromosomes in the GnomAD database, including 550 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 0.076 (550 hom., cov: 32)
• Consequence: NDUFS4 NM_002495.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.36

Genes affected

NDUFS4 (HGNC:7711): (NADH:ubiquinone oxidoreductase subunit S4) This gene encodes an nuclear-encoded accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I, or NADH:ubiquinone oxidoreductase). Complex I removes electrons from NADH and passes them to the electron acceptor ubiquinone. Mutations in this gene can cause mitochondrial complex I deficiencies such as Leigh syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFS4	NM_002495.4	c.98+8205T>C		intron_variant		ENST00000296684.10	NP_002486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFS4	ENST00000296684.10	c.98+8205T>C		intron_variant		1	NM_002495.4	ENSP00000296684	P1

Frequencies

GnomAD3 genomes AF: 0.0758 AC: 11538 AN: 152160 Hom.: 549 Cov.: 32

Gnomad AFR AF: 0.0241

Gnomad AMI AF: 0.0485

Gnomad AMR AF: 0.0917

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0480

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.0757 AC: 11532 AN: 152278 Hom.: 550 Cov.: 32 AF XY: 0.0757 AC XY: 5637 AN XY: 74460

Gnomad4 AFR AF: 0.0241

Gnomad4 AMR AF: 0.0915

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.00250

Gnomad4 SAS AF: 0.0481

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0882 Hom.: 85

Bravo AF: 0.0727

Asia WGS AF: 0.0350 AC: 120 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Benign	0.86

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: rs13156337; hg19: chr5-52864795;