rs371032334

Variant names:

• chr19-1383919-A-C
• rs371032334
• NM_024407.5:c.-8A>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS1

The NM_024407.5(NDUFS7):​c.-8A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00028 in 1,581,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: NDUFS7 NM_024407.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.148
• Publications: 0 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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BP6: Variant 19-1383919-A-C is Benign according to our data. Variant chr19-1383919-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 510979.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00144 (219/152330) while in subpopulation AFR AF = 0.0051 (212/41574). AF 95% confidence interval is 0.00454. There are 0 homozygotes in GnomAd4. There are 98 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: NM_024407.5. 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
	NDUFS7	NM_024407.5	MANE Select	c.-8A>C		5_prime_UTR	Exon 1 of 8	NP_077718.3
	NDUFS7	NM_001363602.2		c.-8A>C		5_prime_UTR	Exon 1 of 8	NP_001350531.1	F5H5N1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFS7	ENST00000233627.14	TSL:1 MANE Select	c.-8A>C		5_prime_UTR	Exon 1 of 8	ENSP00000233627.9	O75251-1
	NDUFS7	ENST00000874016.1		c.-8A>C		5_prime_UTR	Exon 1 of 9	ENSP00000544075.1
	NDUFS7	ENST00000874018.1		c.-8A>C		5_prime_UTR	Exon 1 of 8	ENSP00000544077.1

Frequencies

GnomAD3 genomes AF: 0.00145 AC: 220 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00514

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000392

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000379 AC: 74 AN: 195414 AF XY: 0.000218

Gnomad AFR exome AF: 0.00641

Gnomad AMR exome AF: 0.0000687

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000156 AC: 223 AN: 1429048 Hom.: 0 Cov.: 32 AF XY: 0.000127 AC XY: 90 AN XY: 708048

African (AFR) AF: 0.00596 AC: 195 AN: 32696

American (AMR) AF: 0.000125 AC: 5 AN: 40022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25556

East Asian (EAS) AF: 0.00 AC: 0 AN: 37742

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 81706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49812

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5624

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1096790

Other (OTH) AF: 0.000372 AC: 22 AN: 59100

GnomAD4 genome AF: 0.00144 AC: 219 AN: 152330 Hom.: 0 Cov.: 33 AF XY: 0.00132 AC XY: 98 AN XY: 74498

African (AFR) AF: 0.00510 AC: 212 AN: 41574

American (AMR) AF: 0.000392 AC: 6 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000503 Hom.: 0

Bravo AF: 0.00165

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	16
DANN	Benign	0.83
PhyloP100		0.15
PromoterAI		0.0026	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism

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: rs371032334; hg19: chr19-1383918;