19-5893614-A-T

Position:

• chr19-5893614-A-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.314-324T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0558 in 152,006 control chromosomes in the GnomAD database, including 635 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.056 (635 hom., cov: 32)
• Consequence: NDUFA11 NM_001193375.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.674

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 19-5893614-A-T is Benign according to our data. Variant chr19-5893614-A-T is described in ClinVar as [Benign]. Clinvar id is 1175448.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA11	NM_001193375.3	c.314-324T>A		intron_variant			NP_001180304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000267740	ENST00000586349.5	c.382+2839T>A		intron_variant		2		ENSP00000466639.1
NDUFA11	ENST00000418389.6	c.314-324T>A		intron_variant		2		ENSP00000389160.1
ENSG00000267740	ENST00000585661.1	c.307+2839T>A		intron_variant		2		ENSP00000467210.1
ENSG00000267740	ENST00000592091.5	n.313+2839T>A		intron_variant		2		ENSP00000465499.1

Frequencies

GnomAD3 genomes AF: 0.0557 AC: 8458 AN: 151886 Hom.: 635 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.00721

Gnomad EAS AF: 0.000584

Gnomad SAS AF: 0.0411

Gnomad FIN AF: 0.00452

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00866

Gnomad OTH AF: 0.0464

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0558 AC: 8484 AN: 152006 Hom.: 635 Cov.: 32 AF XY: 0.0544 AC XY: 4042 AN XY: 74324

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.0175

Gnomad4 ASJ AF: 0.00721

Gnomad4 EAS AF: 0.000585

Gnomad4 SAS AF: 0.0413

Gnomad4 FIN AF: 0.00452

Gnomad4 NFE AF: 0.00866

Gnomad4 OTH AF: 0.0478

Alfa AF: 0.0376 Hom.: 61

Bravo AF: 0.0610

Asia WGS AF: 0.0360 AC: 127 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

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.27

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: rs28506987; hg19: chr19-5893625;