19-1383551-G-A

Variant names:

• chr19-1383551-G-A
• rs117758624
• ENST00000546283.5:c.-277G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS1

The ENST00000546283.5(NDUFS7):​c.-277G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000264 in 914,184 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00024 (0 hom.)
• Consequence: NDUFS7 ENST00000546283.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.12
• Publications: 1 publications found

Genes affected

NDUFS7 (HGNC:7714): (NADH:ubiquinone oxidoreductase core subunit S7) This gene encodes a protein that is a subunit of one of the complexes that forms the mitochondrial respiratory chain. This protein is one of over 40 subunits found in complex I, the nicotinamide adenine dinucleotide (NADH):ubiquinone oxidoreductase. This complex functions in the transfer of electrons from NADH to the respiratory chain, and ubiquinone is believed to be the immediate electron acceptor for the enzyme. Mutations in this gene cause Leigh syndrome due to mitochondrial complex I deficiency, a severe neurological disorder that results in bilaterally symmetrical necrotic lesions in subcortical brain regions. [provided by RefSeq, Jul 2008]

NDUFS7 Gene-Disease associations (from GenCC):

• mitochondrial complex I deficiency, nuclear type 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• Leigh syndrome with leukodystrophy

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TRN-GTT2-6 (HGNC:34758):

TRF-GAA1-6 (HGNC:34873):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000394 (60/152356) while in subpopulation AFR AF = 0.00101 (42/41596). AF 95% confidence interval is 0.000768. There are 0 homozygotes in GnomAd4. There are 32 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000546283.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFS7	ENST00000546283.5	TSL:2	c.-277G>A		5_prime_UTR	Exon 1 of 8	ENSP00000440348.1	O75251-2

Frequencies

GnomAD3 genomes AF: 0.000394 AC: 60 AN: 152238 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.000956

GnomAD4 exome AF: 0.000238 AC: 181 AN: 761828 Hom.: 0 Cov.: 10 AF XY: 0.000240 AC XY: 92 AN XY: 383962

African (AFR) AF: 0.00139 AC: 21 AN: 15064

American (AMR) AF: 0.000228 AC: 3 AN: 13148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12732

East Asian (EAS) AF: 0.00 AC: 0 AN: 13524

South Asian (SAS) AF: 0.000450 AC: 27 AN: 59934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2146

European-Non Finnish (NFE) AF: 0.000196 AC: 118 AN: 601658

Other (OTH) AF: 0.000401 AC: 12 AN: 29894

GnomAD4 genome AF: 0.000394 AC: 60 AN: 152356 Hom.: 0 Cov.: 33 AF XY: 0.000429 AC XY: 32 AN XY: 74508

African (AFR) AF: 0.00101 AC: 42 AN: 41596

American (AMR) AF: 0.0000653 AC: 1 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68022

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.0000560 Hom.: 14

Bravo AF: 0.000491

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.0010
DANN	Benign	0.79
PhyloP100		-6.1
PromoterAI		-0.028	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs117758624; hg19: chr19-1383550;