chr19-5892812-G-C

Position:

• chr19-5892812-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001193375.3(NDUFA11):​c.*105C>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 0.00989 in 1,339,710 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (33 hom., cov: 33)
  • Exomes 𝑓: 0.0091 (119 hom.)
• Consequence: NDUFA11 NM_001193375.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.836

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=-0.84).
• BP6: Variant 19-5892812-G-C is Benign according to our data. Variant chr19-5892812-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1318064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0162 (2463/152316) while in subpopulation SAS AF= 0.0396 (191/4828). AF 95% confidence interval is 0.0358. There are 33 homozygotes in gnomad4. There are 1198 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFA11	NM_001193375.3	c.*105C>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+3641C>G		intron_variant		2		ENSP00000466639.1
NDUFA11	ENST00000418389	c.*105C>G		3_prime_UTR_variant	4/4	2		ENSP00000389160.1
ENSG00000267740	ENST00000585661.1	c.307+3641C>G		intron_variant		2		ENSP00000467210.1
ENSG00000267740	ENST00000592091.5	n.313+3641C>G		intron_variant		2		ENSP00000465499.1

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2456 AN: 152198 Hom.: 33 Cov.: 33

Gnomad AFR AF: 0.0373

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00576

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0393

Gnomad FIN AF: 0.00433

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00794

Gnomad OTH AF: 0.0163

GnomAD4 exome AF: 0.00908 AC: 10784 AN: 1187394 Hom.: 119 Cov.: 18 AF XY: 0.00957 AC XY: 5471 AN XY: 571956

Gnomad4 AFR exome AF: 0.0405

Gnomad4 AMR exome AF: 0.00530

Gnomad4 ASJ exome AF: 0.00116

Gnomad4 EAS exome AF: 0.000120

Gnomad4 SAS exome AF: 0.0425

Gnomad4 FIN exome AF: 0.00578

Gnomad4 NFE exome AF: 0.00712

Gnomad4 OTH exome AF: 0.0105

GnomAD4 genome AF: 0.0162 AC: 2463 AN: 152316 Hom.: 33 Cov.: 33 AF XY: 0.0161 AC XY: 1198 AN XY: 74478

Gnomad4 AFR AF: 0.0374

Gnomad4 AMR AF: 0.00569

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0396

Gnomad4 FIN AF: 0.00433

Gnomad4 NFE AF: 0.00794

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0132 Hom.: 1

Bravo AF: 0.0163

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.30
DANN	Benign	0.40

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: rs77060799; hg19: chr19-5892823;