Genetic Variant UQCR11:p.Lys54Asn (chr19-1599449-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006830.4(UQCR11):c.162G>T(p.Lys54Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

UQCR11
NM_006830.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.127

Variant links:

Genes affected

UQCR11 (HGNC:30862): (ubiquinol-cytochrome c reductase, complex III subunit XI) This gene encodes the smallest known component of the ubiquinol-cytochrome c reductase complex, which forms part of the mitochondrial respiratory chain. The encoded protein may function as a binding factor for the iron-sulfur protein in this complex. [provided by RefSeq, Oct 2009]

UQCR11 links:

ENSG00000267059 (HGNC:):

ENSG00000267059 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.017908573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UQCR11	NM_006830.4 link	c.162G>T	p.Lys54Asn	missense_variant	Exon 2 of 3	ENST00000591899.8	NP_006821.1	O14957

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UQCR11	ENST00000591899.8 link	c.162G>T	p.Lys54Asn	missense_variant	Exon 2 of 3	1	NM_006830.4	ENSP00000467262.1		O14957
ENSG00000267059	ENST00000585937.1 link	n.162G>T		non_coding_transcript_exon_variant	Exon 2 of 7	3		ENSP00000468614.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251078

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461448

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152380

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74524

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000659

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.162G>T (p.K54N) alteration is located in exon 2 (coding exon 2) of the UQCR11 gene. This alteration results from a G to T substitution at nucleotide position 162, causing the lysine (K) at amino acid position 54 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.081

T;T;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.67

M_CAP

Benign

0.0093

MetaRNN

Benign

0.018

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.57

Sift4G

Benign

0.15

T;T;T

Polyphen

0.026

B;B;B

Vest4

0.15

MutPred

0.49

Loss of methylation at K54 (P = 0.0189);Loss of methylation at K54 (P = 0.0189);Loss of methylation at K54 (P = 0.0189);

MVP

0.055

MPC

0.43

ClinPred

0.24

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.046

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over