8-144522552-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001024678.4(LRRC24):​c.1465G>A​(p.Ala489Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000724 in 1,533,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

LRRC24
NM_001024678.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.03
Variant links:
Genes affected
LRRC24 (HGNC:28947): (leucine rich repeat containing 24) Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be integral component of membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]
LRRC14 (HGNC:20419): (leucine rich repeat containing 14) This gene encodes a leucine-rich repeat-containing protein. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.07217482).
BS2
High AC in GnomAdExome4 at 107 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRRC24NM_001024678.4 linkc.1465G>A p.Ala489Thr missense_variant Exon 5 of 5 ENST00000529415.7 NP_001019849.2 Q50LG9
LRRC14NM_014665.4 linkc.*1074C>T 3_prime_UTR_variant Exon 4 of 4 ENST00000292524.6 NP_055480.1 Q15048

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRRC24ENST00000529415.7 linkc.1465G>A p.Ala489Thr missense_variant Exon 5 of 5 1 NM_001024678.4 ENSP00000434849.1 Q50LG9
LRRC14ENST00000292524.6 linkc.*1074C>T 3_prime_UTR_variant Exon 4 of 4 1 NM_014665.4 ENSP00000292524.1 Q15048
LRRC24ENST00000533758.1 linkc.1456G>A p.Ala486Thr missense_variant Exon 5 of 5 5 ENSP00000435653.1 G3V1D8
LRRC14ENST00000528528.1 linkn.-30C>T upstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152186
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000723
AC:
10
AN:
138218
Hom.:
0
AF XY:
0.000117
AC XY:
9
AN XY:
77208
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000137
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000136
Gnomad NFE exome
AF:
0.000122
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000775
AC:
107
AN:
1381488
Hom.:
0
Cov.:
32
AF XY:
0.0000762
AC XY:
52
AN XY:
682800
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000632
Gnomad4 NFE exome
AF:
0.0000921
Gnomad4 OTH exome
AF:
0.0000876
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152186
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340
ExAC
AF:
0.0000949
AC:
11

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 01, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1465G>A (p.A489T) alteration is located in exon 5 (coding exon 4) of the LRRC24 gene. This alteration results from a G to A substitution at nucleotide position 1465, causing the alanine (A) at amino acid position 489 to be replaced by a threonine (T). 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
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
5.7
DANN
Benign
0.84
DEOGEN2
Benign
0.0044
T;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.34
T;T
M_CAP
Uncertain
0.24
D
MetaRNN
Benign
0.072
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.90
L;.
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-0.54
N;N
REVEL
Benign
0.038
Sift
Benign
0.38
T;T
Sift4G
Benign
0.38
T;T
Polyphen
0.29
B;B
Vest4
0.13
MutPred
0.11
Gain of phosphorylation at A489 (P = 0.0099);.;
MVP
0.48
MPC
0.31
ClinPred
0.036
T
GERP RS
-2.1
Varity_R
0.030
gMVP
0.042

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.

Other links and lift over

dbSNP: rs768135497; hg19: chr8-145747936; API