Variant 19-54454442-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000326764.10(LENG8):c.439G>A(p.Gly147Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,607,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

LENG8
ENST00000326764.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.27

Variant links:

Genes affected

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

LENG8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.118140996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LENG8	NM_052925.4 linkuse as main transcript	c.439G>A	p.Gly147Ser	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 linkuse as main transcript	c.439G>A	p.Gly147Ser	missense_variant	6/16	1	NM_052925.4	ENSP00000318374	P1	Q96PV6-2
LENG8	ENST00000610347.1 linkuse as main transcript	c.439G>A	p.Gly147Ser	missense_variant	5/14	5		ENSP00000478590
LENG8	ENST00000376514.6 linkuse as main transcript	c.328G>A	p.Gly110Ser	missense_variant	5/14	5		ENSP00000365697
LENG8	ENST00000439657.5 linkuse as main transcript	c.439G>A	p.Gly147Ser	missense_variant	6/8	5		ENSP00000399507

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000408

AC:

AN:

245208

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132794

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS 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:

0.00000275

AC:

AN:

1455248

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723342

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.439G>A (p.G147S) alteration is located in exon 6 (coding exon 5) of the LENG8 gene. This alteration results from a G to A substitution at nucleotide position 439, causing the glycine (G) at amino acid position 147 to be replaced by a serine (S). 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

0.070

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.86

.;.;D;D;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;.;.;.;.

MutationTaster

Benign

0.96

D;D;D;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.85

.;N;D;.;.

REVEL

Benign

0.062

Sift

Benign

0.087

.;T;T;.;.

Sift4G

Benign

0.15

T;T;T;T;T

Vest4

0.26

MutPred

0.25

Gain of phosphorylation at G110 (P = 0.0149);.;.;Gain of phosphorylation at G110 (P = 0.0149);.;

MVP

0.15

MPC

0.35

ClinPred

0.22

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.084

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over