19-5894573-G-A

Position:

• chr19-5894573-G-A

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.314-1283C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 1,373,222 control chromosomes in the GnomAD database, including 4,374 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (337 hom., cov: 33)
  • Exomes 𝑓: 0.077 (4037 hom.)
• Consequence: NDUFA11 NM_001193375.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.66

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=-0.75).
• BP6: Variant 19-5894573-G-A is Benign according to our data. Variant chr19-5894573-G-A is described in ClinVar as [Benign]. Clinvar id is 1228269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDUFA11	NM_001193375.3	c.314-1283C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFA11	ENST00000418389.6	c.314-1283C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0583 AC: 8870 AN: 152078 Hom.: 337 Cov.: 33

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.0473

Gnomad AMR AF: 0.0629

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.0466

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0875

Gnomad OTH AF: 0.0789

GnomAD4 exome AF: 0.0772 AC: 94263 AN: 1221024 Hom.: 4037 AF XY: 0.0755 AC XY: 45764 AN XY: 605838

Gnomad4 AFR exome AF: 0.0188

Gnomad4 AMR exome AF: 0.0493

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.000526

Gnomad4 SAS exome AF: 0.0219

Gnomad4 FIN exome AF: 0.0549

Gnomad4 NFE exome AF: 0.0868

Gnomad4 OTH exome AF: 0.0764

GnomAD4 genome AF: 0.0583 AC: 8870 AN: 152198 Hom.: 337 Cov.: 33 AF XY: 0.0546 AC XY: 4064 AN XY: 74416

Gnomad4 AFR AF: 0.0180

Gnomad4 AMR AF: 0.0628

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0157

Gnomad4 FIN AF: 0.0466

Gnomad4 NFE AF: 0.0875

Gnomad4 OTH AF: 0.0781

Alfa AF: 0.0741 Hom.: 71

Bravo AF: 0.0592

Asia WGS AF: 0.0130 AC: 46 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.9
DANN	Benign	0.96
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.3

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: rs12974991; hg19: chr19-5894584; COSMIC: COSV53136617; COSMIC: COSV53136617;