chr5-53588734-G-A

Position:

• chr5-53588734-G-A

Variant summary

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

The NM_002495.4(NDUFS4):​c.99-14718G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 152,052 control chromosomes in the GnomAD database, including 14,410 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 0.42 (14410 hom., cov: 33)
• Consequence: NDUFS4 NM_002495.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFS4	NM_002495.4	c.99-14718G>A		intron_variant		ENST00000296684.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFS4	ENST00000296684.10	c.99-14718G>A		intron_variant		1	NM_002495.4	P1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64291 AN: 151936 Hom.: 14410 Cov.: 33

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.423 AC: 64308 AN: 152052 Hom.: 14410 Cov.: 33 AF XY: 0.425 AC XY: 31591 AN XY: 74314

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.409

Alfa AF: 0.454 Hom.: 2023

Bravo AF: 0.415

Asia WGS AF: 0.361 AC: 1259 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.4
DANN	Benign	0.28

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: rs2168662; hg19: chr5-52884564;