NM_001004316.3:c.139A>G

Variant names:

• chr3-156852858-A-G
• rs537287455
• NM_001004316.3:c.139A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001004316.3(LEKR1):​c.139A>G​(p.Met47Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000306 in 1,534,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: LEKR1 NM_001004316.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.27
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.042971402).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004316.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LEKR1	NM_001004316.3	MANE Select	c.139A>G	p.Met47Val	missense	Exon 3 of 13	NP_001004316.2	J3KP02
	LEKR1	NM_001193283.2		c.139A>G	p.Met47Val	missense	Exon 3 of 5	NP_001180212.1	Q6ZMV7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LEKR1	ENST00000356539.9	TSL:5 MANE Select	c.139A>G	p.Met47Val	missense	Exon 3 of 13	ENSP00000348936.4	J3KP02
	LEKR1	ENST00000491763.1	TSL:1	c.139A>G	p.Met47Val	missense	Exon 3 of 5	ENSP00000474182.1	Q6ZMV7
	LEKR1	ENST00000477399.5	TSL:2	c.139A>G	p.Met47Val	missense	Exon 3 of 5	ENSP00000425282.1	Q6ZMV7

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152146 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000778 AC: 11 AN: 141476 AF XY: 0.0000264

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000344

Gnomad OTH exome AF: 0.000238

GnomAD4 exome AF: 0.0000304 AC: 42 AN: 1382608 Hom.: 0 Cov.: 29 AF XY: 0.0000352 AC XY: 24 AN XY: 682412

African (AFR) AF: 0.00 AC: 0 AN: 31506

American (AMR) AF: 0.00 AC: 0 AN: 35684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25134

East Asian (EAS) AF: 0.00 AC: 0 AN: 35548

South Asian (SAS) AF: 0.000316 AC: 25 AN: 79136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 0.00000928 AC: 10 AN: 1077114

Other (OTH) AF: 0.000121 AC: 7 AN: 57812

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152264 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74446

African (AFR) AF: 0.00 AC: 0 AN: 41576

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67966

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000502 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Benign	0.92
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.3
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.018
Sift	Benign	0.44	T
Sift4G	Benign	0.41	T
Polyphen		0.0080	B
Vest4		0.30
MutPred		0.35		Gain of catalytic residue at M47 (P = 0.0561)
MVP		0.061
ClinPred		0.019	T
GERP RS		4.2
gMVP		0.037
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs537287455; hg19: chr3-156570647;