rs924644718

Variant names:

• chr3-156920591-A-T
• rs924644718
• NM_001004316.3:c.280A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001004316.3(LEKR1):​c.280A>T​(p.Met94Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000762 in 1,313,090 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: LEKR1 NM_001004316.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.933
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058912158).

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.280A>T	p.Met94Leu	missense	Exon 4 of 13	NP_001004316.2	J3KP02
	LEKR1	NM_001193283.2		c.280A>T	p.Met94Leu	missense	Exon 4 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.280A>T	p.Met94Leu	missense	Exon 4 of 13	ENSP00000348936.4	J3KP02
	LEKR1	ENST00000491763.1	TSL:1	c.280A>T	p.Met94Leu	missense	Exon 4 of 5	ENSP00000474182.1	Q6ZMV7
	LEKR1	ENST00000477399.5	TSL:2	c.280A>T	p.Met94Leu	missense	Exon 4 of 5	ENSP00000425282.1	Q6ZMV7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000762 AC: 10 AN: 1313090 Hom.: 0 Cov.: 24 AF XY: 0.00000461 AC XY: 3 AN XY: 650322

African (AFR) AF: 0.000102 AC: 3 AN: 29480

American (AMR) AF: 0.00 AC: 0 AN: 32036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24568

East Asian (EAS) AF: 0.00 AC: 0 AN: 34808

South Asian (SAS) AF: 0.0000136 AC: 1 AN: 73766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34894

Middle Eastern (MID) AF: 0.000180 AC: 1 AN: 5550

European-Non Finnish (NFE) AF: 9.78e-7 AC: 1 AN: 1022544

Other (OTH) AF: 0.0000721 AC: 4 AN: 55444

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

Asia WGS AF: 0.000579 AC: 2 AN: 3466

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	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	11
DANN	Benign	0.75
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.93
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.020
Sift	Benign	0.52	T
Sift4G	Benign	1.0	T
Polyphen		0.021	B
Vest4		0.31
MutPred		0.29		Gain of catalytic residue at M94 (P = 0.001)
MVP		0.014
ClinPred		0.042	T
GERP RS		3.9
gMVP		0.0059
Mutation Taster		=96/4	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: rs924644718; hg19: chr3-156638380;