19-54462140-C-G

Variant names:

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

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>C​(p.Gly463Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LENG9 NM_001301782.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.16838285).

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>C	p.Gly463Arg	missense	Exon 1 of 1	NP_001288711.1	A0A087WVD1
	LENG8	NM_052925.4	MANE Select	c.*1212C>G		downstream_gene	N/A	NP_443157.1	Q96PV6-2
	LENG8	NM_001375638.1		c.*3234C>G		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>C	p.Gly463Arg	missense	Exon 1 of 1	ENSP00000479355.1	A0A087WVD1
	LENG8	ENST00000326764.10	TSL:1 MANE Select	c.*1212C>G		downstream_gene	N/A	ENSP00000318374.5	Q96PV6-2
	LENG8	ENST00000610347.1	TSL:5	c.*3234C>G		downstream_gene	N/A	ENSP00000478590.1	A0A087WUE4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449462 Hom.: 0 Cov.: 66 AF XY: 0.00 AC XY: 0 AN XY: 719950

African (AFR) AF: 0.00 AC: 0 AN: 33288

American (AMR) AF: 0.00 AC: 0 AN: 43758

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24984

East Asian (EAS) AF: 0.00 AC: 0 AN: 39592

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52690

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105094

Other (OTH) AF: 0.00 AC: 0 AN: 59740

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.30
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	0.14	N
M_CAP	Benign	0.014	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		0.90	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;