3-156979223-T-G

Variant names:

• chr3-156979223-T-G
• rs372814129
• NM_001004316.3:c.775T>G

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.775T>G​(p.Leu259Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000881 in 1,135,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/18 in silico tools predict a benign outcome for this variant. 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. L259I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
• Consequence: LEKR1 NM_001004316.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114
• 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=0.051047534).

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.775T>G	p.Leu259Val	missense	Exon 7 of 13	NP_001004316.2	J3KP02

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LEKR1	ENST00000356539.9	TSL:5 MANE Select	c.775T>G	p.Leu259Val	missense	Exon 7 of 13	ENSP00000348936.4	J3KP02
	LEKR1	ENST00000470811.6	TSL:2	n.775T>G		non_coding_transcript_exon	Exon 7 of 14	ENSP00000418214.2	A0A8I5FW65
	LEKR1	ENST00000489350.5	TSL:3	n.476T>G		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000707 AC: 1 AN: 141450 AF XY: 0.0000132

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000407

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 8.81e-7 AC: 1 AN: 1135248 Hom.: 0 Cov.: 26 AF XY: 0.00000179 AC XY: 1 AN XY: 557216

African (AFR) AF: 0.00 AC: 0 AN: 24362

American (AMR) AF: 0.0000354 AC: 1 AN: 28258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15930

East Asian (EAS) AF: 0.00 AC: 0 AN: 12830

South Asian (SAS) AF: 0.00 AC: 0 AN: 76126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4392

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 917780

Other (OTH) AF: 0.00 AC: 0 AN: 41408

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	17
DANN	Benign	0.93
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.11
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.032
Sift	Benign	0.41	T
Sift4G	Benign	0.23	T
Vest4		0.12
MutPred		0.16		Gain of methylation at K263 (P = 0.0874)
MVP		0.13
ClinPred		0.034	T
GERP RS		0.45
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs372814129; hg19: chr3-156697012;