5-53641979-G-T

Position:

• chr5-53641979-G-T

Variant summary

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

The NM_002495.4(NDUFS4):​c.178-4254G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,952 control chromosomes in the GnomAD database, including 10,214 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 0.35 (10214 hom., cov: 32)
• Consequence: NDUFS4 NM_002495.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

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]

NDUFS4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFS4	NM_002495.4	c.178-4254G>T		intron_variant		ENST00000296684.10	NP_002486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFS4	ENST00000296684.10	c.178-4254G>T		intron_variant		1	NM_002495.4	ENSP00000296684.5

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53187 AN: 151834 Hom.: 10199 Cov.: 32

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.350 AC: 53256 AN: 151952 Hom.: 10214 Cov.: 32 AF XY: 0.349 AC XY: 25955 AN XY: 74280

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.348

Alfa AF: 0.268 Hom.: 2762

Bravo AF: 0.361

Asia WGS AF: 0.413 AC: 1432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.46
DANN	Benign	0.56

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: rs365578; hg19: chr5-52937809;