3-157028233-T-G

Position:

• chr3-157028233-T-G

Variant summary

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

The NM_001004316.3(LEKR1):​c.1499T>G​(p.Leu500Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000024 in 1,461,186 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: LEKR1 NM_001004316.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.89

Genes affected

LEKR1 (HGNC:33765): (leucine, glutamate and lysine rich 1)

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
LEKR1	NM_001004316.3	c.1499T>G	p.Leu500Arg	missense_variant	12/13	ENST00000356539.9	NP_001004316.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LEKR1	ENST00000356539.9	c.1499T>G	p.Leu500Arg	missense_variant	12/13	5	NM_001004316.3	ENSP00000348936	P1
LEKR1	ENST00000470811.6	c.*977T>G		3_prime_UTR_variant, NMD_transcript_variant	13/14	2		ENSP00000418214

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000800 AC: 2 AN: 249862 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135358

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000240 AC: 35 AN: 1461186 Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18 AN XY: 726914

Gnomad4 AFR exome AF: 0.0000299

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: 0.0000306

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Mar 15, 2024

The c.1499T>G (p.L500R) alteration is located in exon 12 (coding exon 11) of the LEKR1 gene. This alteration results from a T to G substitution at nucleotide position 1499, causing the leucine (L) at amino acid position 500 to be replaced by an arginine (R). 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
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;.
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.75	T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Uncertain	-0.054	T
MutationAssessor	Uncertain	2.6	M;.
MutationTaster	Benign	0.98	D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;.
Vest4		0.89
MutPred		0.26		Loss of stability (P = 0.0123);.;
MVP		0.46
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.41

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: rs1177847814; hg19: chr3-156746022;