rs1310922579

Variant names:

• chr8-144522479-C-G
• rs1310922579
• NM_001024678.4:c.1538G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-144522479-C-G
• chr8-144522479-C-T

Variant summary

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

The NM_001024678.4(LRRC24):​c.1538G>C​(p.Cys513Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000752 in 1,330,150 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C513G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: LRRC24 NM_001024678.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.546

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]

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 rank	MANE	Protein	UniProt
LRRC24	NM_001024678.4	c.1538G>C	p.Cys513Ser	missense_variant	Exon 5 of 5	ENST00000529415.7	NP_001019849.2
LRRC14	NM_014665.4	c.*1001C>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000292524.6	NP_055480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC24	ENST00000529415.7	c.1538G>C	p.Cys513Ser	missense_variant	Exon 5 of 5	1	NM_001024678.4	ENSP00000434849.1
LRRC14	ENST00000292524.6	c.*1001C>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_014665.4	ENSP00000292524.1
LRRC24	ENST00000533758.1	c.1529G>C	p.Cys510Ser	missense_variant	Exon 5 of 5	5		ENSP00000435653.1
LRRC14	ENST00000528528.1	n.-103C>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.52e-7 AC: 1 AN: 1330150 Hom.: 0 Cov.: 29 AF XY: 0.00000153 AC XY: 1 AN XY: 655168

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: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000181

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.098	T;.
Eigen	Benign	0.099
Eigen_PC	Benign	0.032
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.63	T;T
M_CAP	Pathogenic	0.37	D
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.54
MutPred		0.37		Gain of relative solvent accessibility (P = 0.0023);.;
MVP		0.23
MPC		1.1
ClinPred		0.98	D
GERP RS		3.8
Varity_R		0.85
gMVP		0.27

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

Other links and lift over

dbSNP: rs1310922579; hg19: chr8-145747863;