3-157028302-A-T

Position:

• chr3-157028302-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004316.3(LEKR1):​c.1568A>T​(p.Glu523Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LEKR1 NM_001004316.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12456545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LEKR1	NM_001004316.3	c.1568A>T	p.Glu523Val	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.1568A>T	p.Glu523Val	missense_variant	12/13	5	NM_001004316.3	ENSP00000348936	P1
LEKR1	ENST00000470811.6	c.*1046A>T		3_prime_UTR_variant, NMD_transcript_variant	13/14	2		ENSP00000418214

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Feb 28, 2024

The c.1568A>T (p.E523V) alteration is located in exon 12 (coding exon 11) of the LEKR1 gene. This alteration results from a A to T substitution at nucleotide position 1568, causing the glutamic acid (E) at amino acid position 523 to be replaced by a valine (V). 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	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.067	T;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.11
Sift	Benign	0.053	T;D
Sift4G	Benign	0.15	T;T
Polyphen		0.47	P;.
Vest4		0.29
MutPred		0.12		Loss of methylation at K223 (P = 0.0808);.;
MVP		0.32
ClinPred		0.92	D
GERP RS		3.1
Varity_R		0.12

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: chr3-156746091;