chr8-144522816-C-T

Position:

chr8-144522816-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001024678.4(LRRC24):c.1201G>A(p.Val401Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000355 in 1,492,932 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

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

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

LRRC24
NM_001024678.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.115

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:

LRRC14 (HGNC:):

LRRC14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0318245).

BS2

High AC in GnomAdExome4 at 50 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC24	NM_001024678.4 linkuse as main transcript	c.1201G>A	p.Val401Met	missense_variant	5/5	ENST00000529415.7	NP_001019849.2	Q50LG9
LRRC14	NM_014665.4 linkuse as main transcript	c.*1338C>T		3_prime_UTR_variant	4/4	ENST00000292524.6	NP_055480.1	Q15048

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LRRC24	ENST00000529415.7 linkuse as main transcript	c.1201G>A	p.Val401Met	missense_variant	5/5	1	NM_001024678.4	ENSP00000434849.1	Q50LG9
LRRC14	ENST00000292524.6 linkuse as main transcript	c.*1338C>T		3_prime_UTR_variant	4/4	1	NM_014665.4	ENSP00000292524.1	Q15048
LRRC24	ENST00000533758.1 linkuse as main transcript	c.1192G>A	p.Val398Met	missense_variant	5/5	5		ENSP00000435653.1	G3V1D8
LRRC14	ENST00000528528.1 linkuse as main transcript	n.235C>T		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151970

Hom.:

Cov.:

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:

0.000193

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000137

AC:

AN:

94768

Hom.:

AF XY:

0.000166

AC XY:

AN XY:

54114

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 SAS exome

AF:

0.000725

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000373

AC:

AN:

1340962

Hom.:

Cov.:

AF XY:

0.0000500

AC XY:

AN XY:

660382

show subpopulations

Gnomad4 AFR exome

AF:

0.0000366

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000333

Gnomad4 SAS exome

AF:

0.000640

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151970

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000413

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000634

AC:

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

Jul 09, 2024

The c.1201G>A (p.V401M) 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 1201, causing the valine (V) at amino acid position 401 to be replaced by a methionine (M). 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

0.091

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0032

T;.

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.25

T;T

M_CAP

Pathogenic

0.29

MetaRNN

Benign

0.032

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

0.46

N;N

REVEL

Benign

0.073

Sift

Benign

0.17

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.0

B;B

Vest4

0.11

MutPred

0.47

Gain of disorder (P = 0.0407);.;

MVP

0.21

MPC

0.33

ClinPred

0.080

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.035

gMVP

0.32

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