1-165563745-C-T

Variant names:

• chr1-165563745-C-T
• NM_001005214.4:c.863C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001005214.4(LRRC52):​c.863C>T​(p.Ala288Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRC52 NM_001005214.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.104

Genes affected

LRRC52 (HGNC:32156): (leucine rich repeat containing 52) Enables potassium channel activator activity; transmembrane transporter binding activity; and voltage-gated potassium channel activity. Involved in positive regulation of voltage-gated potassium channel activity and potassium ion transmembrane transport. Part of voltage-gated potassium channel complex. [provided by Alliance of Genome Resources, Apr 2022]

LRRC52-AS1 (HGNC:54044): (LRRC52 antisense RNA 1)

ACMG classification

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=0.04636705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC52	NM_001005214.4	c.863C>T	p.Ala288Val	missense_variant	Exon 2 of 2	ENST00000294818.2	NP_001005214.2
LRRC52-AS1	NR_026744.2	n.959+10273G>A		intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC52	ENST00000294818.2	c.863C>T	p.Ala288Val	missense_variant	Exon 2 of 2	1	NM_001005214.4	ENSP00000294818.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.863C>T (p.A288V) alteration is located in exon 2 (coding exon 2) of the LRRC52 gene. This alteration results from a C to T substitution at nucleotide position 863, causing the alanine (A) at amino acid position 288 to be replaced by a valine (V). 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	0.075
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.3
DANN	Benign	0.95
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.087
Sift	Benign	0.24	T
Sift4G	Benign	0.25	T
Polyphen		0.035	B
Vest4		0.072
MutPred		0.055		Loss of disorder (P = 0.1475);
MVP		0.64
MPC		0.19
ClinPred		0.14	T
GERP RS		0.54
Varity_R		0.033
gMVP		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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-165532982; COSMIC: COSV54232271;