19-1384247-C-T

Variant names:

• chr19-1384247-C-T
• rs11668291
• NM_024407.5:c.16+305C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_024407.5(NDUFS7):​c.16+305C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 462,998 control chromosomes in the GnomAD database, including 228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (63 hom., cov: 33)
  • Exomes 𝑓: 0.028 (165 hom.)
• Consequence: NDUFS7 NM_024407.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.931

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 19-1384247-C-T is Benign according to our data. Variant chr19-1384247-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 671566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0246 (3743/152298) while in subpopulation NFE AF= 0.0347 (2362/68018). AF 95% confidence interval is 0.0336. There are 63 homozygotes in gnomad4. There are 1798 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 63 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFS7	NM_024407.5	c.16+305C>T		intron_variant	Intron 1 of 7	ENST00000233627.14	NP_077718.3
NDUFS7	NM_001363602.2	c.16+305C>T		intron_variant	Intron 1 of 7		NP_001350531.1
NDUFS7	XM_017026768.3	c.16+305C>T		intron_variant	Intron 1 of 3		XP_016882257.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFS7	ENST00000233627.14	c.16+305C>T		intron_variant	Intron 1 of 7	1	NM_024407.5	ENSP00000233627.9

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 3745 AN: 152180 Hom.: 63 Cov.: 33

Gnomad AFR AF: 0.00598

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.0249

Gnomad ASJ AF: 0.0547

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.0362

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0347

Gnomad OTH AF: 0.0378

GnomAD4 exome AF: 0.0285 AC: 8840 AN: 310700 Hom.: 165 AF XY: 0.0287 AC XY: 4680 AN XY: 163190

Gnomad4 AFR exome AF: 0.00913

Gnomad4 AMR exome AF: 0.0170

Gnomad4 ASJ exome AF: 0.0573

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0120

Gnomad4 FIN exome AF: 0.0314

Gnomad4 NFE exome AF: 0.0328

Gnomad4 OTH exome AF: 0.0274

GnomAD4 genome AF: 0.0246 AC: 3743 AN: 152298 Hom.: 63 Cov.: 33 AF XY: 0.0241 AC XY: 1798 AN XY: 74472

Gnomad4 AFR AF: 0.00597

Gnomad4 AMR AF: 0.0248

Gnomad4 ASJ AF: 0.0547

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0101

Gnomad4 FIN AF: 0.0362

Gnomad4 NFE AF: 0.0347

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0295 Hom.: 5

Bravo AF: 0.0223

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.8
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs11668291; hg19: chr19-1384246;