Variant 1-165544616-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001005214.4(LRRC52):c.320A>C(p.Asp107Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LRRC52
NM_001005214.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.71

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 links:

LRRC52-AS1 (HGNC:):

LRRC52-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.871

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC52	NM_001005214.4 linkuse as main transcript	c.320A>C	p.Asp107Ala	missense_variant	1/2	ENST00000294818.2	NP_001005214.2	Q8N7C0
LRRC52-AS1	NR_026744.2 linkuse as main transcript	n.960-21529T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC52	ENST00000294818.2 linkuse as main transcript	c.320A>C	p.Asp107Ala	missense_variant	1/2	1	NM_001005214.4	ENSP00000294818.2		Q8N7C0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251452

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135892

show subpopulations

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:

6.84e-7

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2024

The c.320A>C (p.D107A) alteration is located in exon 1 (coding exon 1) of the LRRC52 gene. This alteration results from a A to C substitution at nucleotide position 320, causing the aspartic acid (D) at amino acid position 107 to be replaced by an alanine (A). 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

Pathogenic

0.72

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.73

M_CAP

Benign

0.024

MetaRNN

Pathogenic

0.87

MetaSVM

Benign

-0.64

MutationAssessor

Pathogenic

3.3

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-6.9

REVEL

Uncertain

0.52

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0050

Polyphen

0.98

Vest4

0.85

MutPred

0.53

Loss of stability (P = 0.0776);

MVP

0.92

MPC

0.82

ClinPred

0.97

GERP RS

5.7

Varity_R

0.84

gMVP

0.81

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

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