1-15807565-G-A

Position:

• chr1-15807565-G-A

Variant summary

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

The NM_001089591.2(UQCRHL):​c.85C>T​(p.Pro29Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: UQCRHL NM_001089591.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.75

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=0.40225914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UQCRHL	NM_001089591.2	c.85C>T	p.Pro29Ser	missense_variant	1/1	ENST00000696689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UQCRHL	ENST00000696689.1	c.85C>T	p.Pro29Ser	missense_variant	1/1		NM_001089591.2	P1
UQCRHL	ENST00000483273.2	c.85C>T	p.Pro29Ser	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251460 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135908

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

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: 0.00000274 AC: 4 AN: 1461888 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

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

Jun 16, 2023

The c.85C>T (p.P29S) alteration is located in exon 1 (coding exon 1) of the UQCRHL gene. This alteration results from a C to T substitution at nucleotide position 85, causing the proline (P) at amino acid position 29 to be replaced by a serine (S). 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	0.18
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	21
DANN	Benign	0.88
DEOGEN2	Benign	0.33	T
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.40	T
PrimateAI	Uncertain	0.58	T
Sift4G	Uncertain	0.043	D
Vest4		0.32
MVP		0.27
GERP RS		0.96
Varity_R		0.068
gMVP		0.35

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: rs1304830462; hg19: chr1-16134060;