19-5892786-T-C

Position:

• chr19-5892786-T-C

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.*131A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0434 in 1,197,750 control chromosomes in the GnomAD database, including 1,356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (160 hom., cov: 33)
  • Exomes 𝑓: 0.045 (1196 hom.)
• Consequence: NDUFA11 NM_001193375.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.118

Genes affected

ENSG00000267740 (HGNC:):

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=-0.82).
• BP6: Variant 19-5892786-T-C is Benign according to our data. Variant chr19-5892786-T-C is described in ClinVar as [Benign]. Clinvar id is 1271140.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA11	NM_001193375.3	c.*131A>G		3_prime_UTR_variant	4/4		NP_001180304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000267740	ENST00000586349.5	c.382+3667A>G		intron_variant		2		ENSP00000466639.1
NDUFA11	ENST00000418389	c.*131A>G		3_prime_UTR_variant	4/4	2		ENSP00000389160.1
ENSG00000267740	ENST00000585661.1	c.307+3667A>G		intron_variant		2		ENSP00000467210.1
ENSG00000267740	ENST00000592091.5	n.313+3667A>G		intron_variant		2		ENSP00000465499.1

Frequencies

GnomAD3 genomes AF: 0.0359 AC: 5453 AN: 152090 Hom.: 160 Cov.: 33

Gnomad AFR AF: 0.00792

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.0245

Gnomad ASJ AF: 0.0874

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00725

Gnomad FIN AF: 0.0509

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0527

Gnomad OTH AF: 0.0373

GnomAD4 exome AF: 0.0445 AC: 46566 AN: 1045542 Hom.: 1196 Cov.: 14 AF XY: 0.0443 AC XY: 22430 AN XY: 505824

Gnomad4 AFR exome AF: 0.00605

Gnomad4 AMR exome AF: 0.0260

Gnomad4 ASJ exome AF: 0.0922

Gnomad4 EAS exome AF: 0.000157

Gnomad4 SAS exome AF: 0.00669

Gnomad4 FIN exome AF: 0.0549

Gnomad4 NFE exome AF: 0.0483

Gnomad4 OTH exome AF: 0.0428

GnomAD4 genome AF: 0.0358 AC: 5449 AN: 152208 Hom.: 160 Cov.: 33 AF XY: 0.0346 AC XY: 2576 AN XY: 74424

Gnomad4 AFR AF: 0.00790

Gnomad4 AMR AF: 0.0245

Gnomad4 ASJ AF: 0.0874

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00705

Gnomad4 FIN AF: 0.0509

Gnomad4 NFE AF: 0.0527

Gnomad4 OTH AF: 0.0365

Alfa AF: 0.0487 Hom.: 37

Bravo AF: 0.0332

Asia WGS AF: 0.00779 AC: 28 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 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.9
DANN	Benign	0.46
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: rs72989069; hg19: chr19-5892797;