dbSNP rs377237052: LRRC24:p.Gln458Arg (chr8-144522644-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001024678.4(LRRC24):c.1373A>G(p.Gln458Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000315 in 1,585,606 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LRRC24
NM_001024678.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.99

Publications

0 publications found

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]

LRRC24 links:

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]

LRRC14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001024678.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC24	NM_001024678.4	MANE Select	c.1373A>G	p.Gln458Arg	missense	Exon 5 of 5	NP_001019849.2	Q50LG9
LRRC14	NM_014665.4	MANE Select	c.*1166T>C		3_prime_UTR	Exon 4 of 4	NP_055480.1	Q15048
LRRC14	NM_001272036.2		c.*1166T>C		3_prime_UTR	Exon 5 of 5	NP_001258965.1	Q15048

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LRRC24	ENST00000529415.7	TSL:1 MANE Select	c.1373A>G	p.Gln458Arg	missense	Exon 5 of 5	ENSP00000434849.1	Q50LG9
LRRC14	ENST00000292524.6	TSL:1 MANE Select	c.*1166T>C		3_prime_UTR	Exon 4 of 4	ENSP00000292524.1	Q15048
LRRC24	ENST00000533758.1	TSL:5	c.1364A>G	p.Gln455Arg	missense	Exon 5 of 5	ENSP00000435653.1	G3V1D8

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000491

AC:

AN:

203752

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000111

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1433398

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

711868

show subpopulations

African (AFR)

AF:

0.0000323

AC:

AN:

30958

American (AMR)

AF:

0.00

AC:

AN:

41978

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25390

East Asian (EAS)

AF:

0.00

AC:

AN:

36734

South Asian (SAS)

AF:

0.00

AC:

AN:

82712

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

9.09e-7

AC:

AN:

1100104

Other (OTH)

AF:

0.00

AC:

AN:

59192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41466

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.00000834

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.87

M_CAP

Pathogenic

0.60

MetaRNN

Uncertain

0.53

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.0

PhyloP100

2.0

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.7

REVEL

Benign

0.24

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.43

MVP

0.78

MPC

1.1

ClinPred

0.96

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.72

gMVP

0.61

Mutation Taster

=43/57

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over