chr19-54462272-C-G

Variant names:

• chr19-54462272-C-G
• rs756283596
• NM_001301782.2:c.1255G>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.1255G>C​(p.Gly419Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,076 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. 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LENG9 NM_001301782.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.520
• 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=0.07570359).

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.1255G>C	p.Gly419Arg	missense	Exon 1 of 1	NP_001288711.1	A0A087WVD1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LENG9	ENST00000611161.2	TSL:6 MANE Select	c.1255G>C	p.Gly419Arg	missense	Exon 1 of 1	ENSP00000479355.1	A0A087WVD1
	LENG8	ENST00000886965.1		c.*1344C>G		downstream_gene	N/A	ENSP00000557024.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1456076 Hom.: 0 Cov.: 68 AF XY: 0.00 AC XY: 0 AN XY: 723868

African (AFR) AF: 0.00 AC: 0 AN: 33396

American (AMR) AF: 0.00 AC: 0 AN: 44368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25582

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85486

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108680

Other (OTH) AF: 0.0000166 AC: 1 AN: 60104

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.17	N
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.52
PrimateAI	Benign	0.27	T
Sift4G	Benign	0.29	T
Vest4		0.11
MVP		0.18
ClinPred		0.45	T
GERP RS		1.9
gMVP		0.37
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: rs756283596; hg19: chr19-54973452;