chr8-144522480-A-C

Position:

• chr8-144522480-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001024678.4(LRRC24):​c.1537T>G​(p.Cys513Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: LRRC24 NM_001024678.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13

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]

LRRC14 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC24	NM_001024678.4	c.1537T>G	p.Cys513Gly	missense_variant	5/5	ENST00000529415.7	NP_001019849.2
LRRC14	NM_014665.4	c.*1002A>C		3_prime_UTR_variant	4/4	ENST00000292524.6	NP_055480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC24	ENST00000529415.7	c.1537T>G	p.Cys513Gly	missense_variant	5/5	1	NM_001024678.4	ENSP00000434849.1
LRRC14	ENST00000292524.6	c.*1002A>C		3_prime_UTR_variant	4/4	1	NM_014665.4	ENSP00000292524.1
LRRC24	ENST00000533758.1	c.1528T>G	p.Cys510Gly	missense_variant	5/5	5		ENSP00000435653.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2024

The c.1537T>G (p.C513G) alteration is located in exon 5 (coding exon 4) of the LRRC24 gene. This alteration results from a T to G substitution at nucleotide position 1537, causing the cysteine (C) at amino acid position 513 to be replaced by a glycine (G). 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	0.26
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.091	T;.
Eigen	Benign	0.079
Eigen_PC	Benign	0.0080
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.63	T;T
M_CAP	Pathogenic	0.44	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.56
MutPred		0.45		Gain of relative solvent accessibility (P = 0.0023);.;
MVP		0.30
MPC		1.1
ClinPred		0.95	D
GERP RS		3.5
Varity_R		0.85
gMVP		0.25

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: chr8-145747864;