19-54462140-C-T

Variant names:

• chr19-54462140-C-T
• rs2084601008
• NM_001301782.2:c.1387G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001301782.2(LENG9):​c.1387G>A​(p.Gly463Arg) 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. 12/17 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LENG9 NM_001301782.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158
• Publications: 0 publications found

Genes affected

LENG9 (HGNC:16306): (leukocyte receptor cluster member 9) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

LENG8 (HGNC:15500): (leukocyte receptor cluster member 8) Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16851604).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301782.2. 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
	LENG9	NM_001301782.2	MANE Select	c.1387G>A	p.Gly463Arg	missense	Exon 1 of 1	NP_001288711.1	A0A087WVD1
	LENG8	NM_052925.4	MANE Select	c.*1212C>T		downstream_gene	N/A	NP_443157.1	Q96PV6-2
	LENG8	NM_001375638.1		c.*3234C>T		downstream_gene	N/A	NP_001362567.1	A0A087WUE4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LENG9	ENST00000611161.2	TSL:6 MANE Select	c.1387G>A	p.Gly463Arg	missense	Exon 1 of 1	ENSP00000479355.1	A0A087WVD1
	LENG8	ENST00000326764.10	TSL:1 MANE Select	c.*1212C>T		downstream_gene	N/A	ENSP00000318374.5	Q96PV6-2
	LENG8	ENST00000610347.1	TSL:5	c.*3234C>T		downstream_gene	N/A	ENSP00000478590.1	A0A087WUE4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 66

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.11	N
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.96	T
PhyloP100		0.16
PrimateAI	Benign	0.43	T
Sift4G	Pathogenic	0.0	D
Vest4		0.29
MVP		0.099
ClinPred		0.91	D
GERP RS		2.6
gMVP		0.54
Mutation Taster		=100/0	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: rs2084601008; hg19: chr19-54973320;