1-15807516-T-A

Position:

• chr1-15807516-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001089591.2(UQCRHL):​c.134A>T​(p.Lys45Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UQCRHL NM_001089591.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.29

Genes affected

UQCRHL (HGNC:51714): (ubiquinol-cytochrome c reductase hinge protein like) This gene has characteristics of a pseudogene derived from the UQCRH gene. However, there is still an open reading frame that could produce a protein of the same or nearly the same size as that of the UQCRH gene, so this gene is being called protein-coding for now. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28907216).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UQCRHL	NM_001089591.2	c.134A>T	p.Lys45Met	missense_variant	1/1	ENST00000696689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UQCRHL	ENST00000696689.1	c.134A>T	p.Lys45Met	missense_variant	1/1		NM_001089591.2	P1
UQCRHL	ENST00000483273.2	c.134A>T	p.Lys45Met	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

The c.134A>T (p.K45M) alteration is located in exon 1 (coding exon 1) of the UQCRHL gene. This alteration results from a A to T substitution at nucleotide position 134, causing the lysine (K) at amino acid position 45 to be replaced by a methionine (M). 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	0.16
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Benign	0.82
DEOGEN2	Benign	0.29	T
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.95	D
MetaRNN	Benign	0.29	T
PrimateAI	Uncertain	0.71	T
Sift4G	Benign	0.081	T
Vest4		0.25
MVP		0.27
GERP RS		1.9
Varity_R		0.13
gMVP		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: rs2069939356; hg19: chr1-16134011;