Genetic Variant LENG8:p.Pro242His (chr19-54454996-C-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_052925.4(LENG8):c.725C>A(p.Pro242His) variant causes a missense change. The variant allele was found at a frequency of 0.0000434 in 1,614,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

LENG8
NM_052925.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.35

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3697061).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LENG8	NM_052925.4 link	c.725C>A	p.Pro242His	missense_variant	Exon 7 of 16	ENST00000326764.10	NP_443157.1	Q96PV6-2A0A024R4R9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LENG8	ENST00000326764.10 link	c.725C>A	p.Pro242His	missense_variant	Exon 7 of 16	1	NM_052925.4	ENSP00000318374.5	Q96PV6-2
LENG8	ENST00000610347.1 link	c.725C>A	p.Pro242His	missense_variant	Exon 6 of 14	5		ENSP00000478590.1	A0A087WUE4
LENG8	ENST00000376514.6 link	c.614C>A	p.Pro205His	missense_variant	Exon 6 of 14	5		ENSP00000365697.3	C9JMY0
LENG8	ENST00000439657.5 link	c.725C>A	p.Pro242His	missense_variant	Exon 7 of 8	5		ENSP00000399507.1	E7EWC7

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000597

AC:

AN:

251398

AF XY:

0.0000442

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000239

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.000896

AC:

AN:

33480

American (AMR)

AF:

0.0000894

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112008

Other (OTH)

AF:

0.0000166

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000230

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.000748

AC:

AN:

41448

American (AMR)

AF:

0.000196

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000685

Hom.:

Bravo

AF:

0.000200

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 09, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.725C>A (p.P242H) alteration is located in exon 7 (coding exon 6) of the LENG8 gene. This alteration results from a C to A substitution at nucleotide position 725, causing the proline (P) at amino acid position 242 to be replaced by a histidine (H). 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

Pathogenic

0.59

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.88

.;.;D;D;D

M_CAP

Benign

0.077

MetaRNN

Benign

0.37

T;T;T;T;T

MetaSVM

Benign

-0.34

MutationAssessor

Uncertain

2.4

M;.;.;.;.

PhyloP100

4.4

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-4.3

.;D;D;.;.

REVEL

Uncertain

0.38

Sift

Pathogenic

0.0

.;D;D;.;.

Sift4G

Uncertain

0.016

D;D;D;D;D

Vest4

0.80

MVP

0.22

MPC

1.2

ClinPred

0.61

GERP RS

5.2

Varity_R

0.70

gMVP

0.40

Mutation Taster

=43/57

disease causing

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over