19-54454470-C-T

Position:

• chr19-54454470-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052925.4(LENG8):​c.467C>T​(p.Ala156Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 6.8e-7 (0 hom.)
• Consequence: LENG8 NM_052925.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.273

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060077727).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LENG8	NM_052925.4	c.467C>T	p.Ala156Val	missense_variant	6/16	ENST00000326764.10	NP_443157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LENG8	ENST00000326764.10	c.467C>T	p.Ala156Val	missense_variant	6/16	1	NM_052925.4	ENSP00000318374.5
LENG8	ENST00000610347.1	c.467C>T	p.Ala156Val	missense_variant	5/14	5		ENSP00000478590.1
LENG8	ENST00000376514.6	c.356C>T	p.Ala119Val	missense_variant	5/14	5		ENSP00000365697.3
LENG8	ENST00000439657.5	c.467C>T	p.Ala156Val	missense_variant	6/8	5		ENSP00000399507.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460914 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726756

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 16, 2024

The c.467C>T (p.A156V) alteration is located in exon 6 (coding exon 5) of the LENG8 gene. This alteration results from a C to T substitution at nucleotide position 467, causing the alanine (A) at amino acid position 156 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Uncertain	1.0
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.83	.;.;T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.060	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.;.;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.88	.;N;N;.;.
REVEL	Benign	0.022
Sift	Uncertain	0.0060	.;D;D;.;.
Sift4G	Benign	0.26	T;T;T;T;T
Vest4		0.36
MutPred		0.20		Loss of glycosylation at P120 (P = 0.1082);.;.;Loss of glycosylation at P120 (P = 0.1082);.;
MVP		0.12
MPC		0.37
ClinPred		0.25	T
GERP RS		3.0
Varity_R		0.060
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-54965649;