19-5892759-C-T

Position:

• chr19-5892759-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001193375.3(NDUFA11):​c.*158G>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 0.59 in 996,398 control chromosomes in the GnomAD database, including 175,336 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.56 (24283 hom., cov: 32)
  • Exomes 𝑓: 0.60 (151053 hom.)
• Consequence: NDUFA11 NM_001193375.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.09

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-5892759-C-T is Benign according to our data. Variant chr19-5892759-C-T is described in ClinVar as [Benign]. Clinvar id is 1240786.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFA11	NM_001193375.3	c.*158G>A		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFA11	ENST00000418389.6	c.*158G>A		3_prime_UTR_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84976 AN: 151896 Hom.: 24270 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.557

GnomAD4 exome AF: 0.595 AC: 502670 AN: 844384 Hom.: 151053 Cov.: 11 AF XY: 0.597 AC XY: 246495 AN XY: 413146

Gnomad4 AFR exome AF: 0.444

Gnomad4 AMR exome AF: 0.715

Gnomad4 ASJ exome AF: 0.515

Gnomad4 EAS exome AF: 0.732

Gnomad4 SAS exome AF: 0.620

Gnomad4 FIN exome AF: 0.517

Gnomad4 NFE exome AF: 0.595

Gnomad4 OTH exome AF: 0.583

GnomAD4 genome AF: 0.559 AC: 85031 AN: 152014 Hom.: 24283 Cov.: 32 AF XY: 0.564 AC XY: 41875 AN XY: 74290

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.589

Gnomad4 OTH AF: 0.557

Alfa AF: 0.531 Hom.: 4267

Bravo AF: 0.565

Asia WGS AF: 0.614 AC: 2134 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.47
DANN	Benign	0.84
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: rs1631032; hg19: chr19-5892770; COSMIC: COSV53137961; COSMIC: COSV53137961;