1-165563745-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.104
Variant links:
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)

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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=0.04636705).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRRC52NM_001005214.4 linkc.863C>T p.Ala288Val missense_variant Exon 2 of 2 ENST00000294818.2 NP_001005214.2 Q8N7C0
LRRC52-AS1NR_026744.2 linkn.959+10273G>A intron_variant Intron 3 of 6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRRC52ENST00000294818.2 linkc.863C>T p.Ala288Val missense_variant Exon 2 of 2 1 NM_001005214.4 ENSP00000294818.2 Q8N7C0

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
LINK: link

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; API