X-154477981-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006014.5(LAGE3):c.395G>A(p.Arg132Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000409 in 1,210,902 control chromosomes in the GnomAD database, including 1 homozygotes. There are 172 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., 16 hem., cov: 24)

Exomes 𝑓: 0.00041 ( 1 hom. 156 hem. )

Consequence

LAGE3
NM_006014.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.246

Publications

1 publications found

Variant links:

Genes affected

LAGE3 (HGNC:26058): (L antigen family member 3) This gene belongs to the ESO/LAGE gene family, members of which are clustered together on chromosome Xq28, and have similar exon-intron structures. Unlike the other family members which are normally expressed only in testis and activated in a wide range of human tumors, this gene is ubiquitously expressed in somatic tissues. The latter, combined with the finding that it is highly conserved in mouse and rat, suggests that the encoded protein is functionally important. An intronless pseudogene with high sequence similarity to this gene is located on chromosome 9. [provided by RefSeq, Jul 2008]

LAGE3 links:

PLXNA3 (HGNC:9101): (plexin A3) This gene encodes a member of the plexin class of proteins. The encoded protein is a class 3 semaphorin receptor, and may be involved in cytoskeletal remodeling and as well as apoptosis. Studies of a similar gene in zebrafish suggest that it is important for axon pathfinding in the developing nervous system. This gene may be associated with tumor progression. [provided by RefSeq, Aug 2013]

PLXNA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009845108).

BP6

Variant X-154477981-C-T is Benign according to our data. Variant chrX-154477981-C-T is described in ClinVar as Benign. ClinVar VariationId is 715992.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 16 XL,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006014.5. 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
	LAGE3	NM_006014.5	MANE Select	c.395G>A	p.Arg132Gln	missense	Exon 3 of 3	NP_006005.2
	PLXNA3	NM_017514.5	MANE Select	c.*5296C>T		downstream_gene	N/A	NP_059984.3	P51805

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAGE3	ENST00000357360.5	TSL:1 MANE Select	c.395G>A	p.Arg132Gln	missense	Exon 3 of 3	ENSP00000349923.4	Q14657
	PLXNA3	ENST00000369682.4	TSL:1 MANE Select	c.*5296C>T		downstream_gene	N/A	ENSP00000358696.3	P51805

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

112896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000932

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0107

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000563

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000999

AC:

183

AN:

183107

AF XY:

0.000975

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0125

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000612

Gnomad OTH exome

AF:

0.000664

GnomAD4 exome

AF:

0.000411

AC:

451

AN:

1097951

Hom.:

Cov.:

AF XY:

0.000429

AC XY:

156

AN XY:

363317

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26396

American (AMR)

AF:

0.00

AC:

AN:

35202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19386

East Asian (EAS)

AF:

0.0140

AC:

422

AN:

30201

South Asian (SAS)

AF:

0.0000739

AC:

AN:

54135

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40521

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.0000154

AC:

AN:

841902

Other (OTH)

AF:

0.000239

AC:

AN:

46078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.000390

AC:

AN:

112951

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

35111

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31146

American (AMR)

AF:

0.0000931

AC:

AN:

10740

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.0110

AC:

AN:

3627

South Asian (SAS)

AF:

0.00

AC:

AN:

2810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6208

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.0000563

AC:

AN:

53326

Other (OTH)

AF:

0.00

AC:

AN:

1536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000863

Hom.:

Bravo

AF:

0.000839

ExAC

AF:

0.000947

AC:

115

EpiCase

AF:

0.00

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.7

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.019

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0098

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

-0.25

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.55

REVEL

Benign

0.084

Sift

Benign

0.34

Sift4G

Benign

0.17

Polyphen

0.64

Vest4

0.020

MVP

0.71

MPC

0.27

ClinPred

0.017

GERP RS

-3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.078

gMVP

0.59

Mutation Taster

=97/3

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over