19-5892732-C-T

Position:

• chr19-5892732-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001193375.3(NDUFA11):​c.*185G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 792,222 control chromosomes in the GnomAD database, including 79,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (12309 hom., cov: 33)
  • Exomes 𝑓: 0.45 (67250 hom.)
• Consequence: NDUFA11 NM_001193375.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0830

Genes affected

NDUFA11 (HGNC:20371): (NADH:ubiquinone oxidoreductase subunit A11) This gene encodes a subunit of the membrane-bound mitochondrial complex I. Complex I is composed of numerous subunits and functions as the NADH-ubiquinol reductase of the mitochondrial electron transport chain. Mutations in this gene are associated with severe mitochondrial complex I deficiency. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 19-5892732-C-T is Benign according to our data. Variant chr19-5892732-C-T is described in ClinVar as [Benign]. Clinvar id is 1280587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFA11	NM_001193375.3	c.*185G>A		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFA11	ENST00000418389.6	c.*185G>A		3_prime_UTR_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55117 AN: 151978 Hom.: 12299 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.341

GnomAD4 exome AF: 0.449 AC: 287389 AN: 640126 Hom.: 67250 Cov.: 9 AF XY: 0.450 AC XY: 141774 AN XY: 315382

Gnomad4 AFR exome AF: 0.0915

Gnomad4 AMR exome AF: 0.545

Gnomad4 ASJ exome AF: 0.378

Gnomad4 EAS exome AF: 0.725

Gnomad4 SAS exome AF: 0.472

Gnomad4 FIN exome AF: 0.410

Gnomad4 NFE exome AF: 0.447

Gnomad4 OTH exome AF: 0.423

GnomAD4 genome AF: 0.363 AC: 55136 AN: 152096 Hom.: 12309 Cov.: 33 AF XY: 0.371 AC XY: 27580 AN XY: 74350

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.344

Alfa AF: 0.429 Hom.: 14873

Bravo AF: 0.357

Asia WGS AF: 0.511 AC: 1774 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.7
DANN	Benign	0.92
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: rs10432306; hg19: chr19-5892743;