X-154478014-A-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006014.5(LAGE3):c.362T>G(p.Ile121Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000884 in 113,138 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. I121T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000088 ( 0 hom., 0 hem., cov: 24)

Consequence

LAGE3
NM_006014.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.481

Publications

2 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:

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ACMG classification

Classification was made for transcript

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=0.24936843).

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.362T>G	p.Ile121Ser	missense	Exon 3 of 3	NP_006005.2
	PLXNA3	NM_017514.5	MANE Select	c.*5329A>C		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.362T>G	p.Ile121Ser	missense	Exon 3 of 3	ENSP00000349923.4	Q14657
	PLXNA3	ENST00000369682.4	TSL:1 MANE Select	c.*5329A>C		downstream_gene	N/A	ENSP00000358696.3	P51805

Frequencies

GnomAD3 genomes

AF:

0.00000884

AC:

AN:

113138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000275

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

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000884

AC:

AN:

113138

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35258

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31167

American (AMR)

AF:

0.00

AC:

AN:

10756

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2658

East Asian (EAS)

AF:

0.000275

AC:

AN:

3640

South Asian (SAS)

AF:

0.00

AC:

AN:

2837

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6251

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53377

Other (OTH)

AF:

0.00

AC:

AN:

1525

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.0097

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.72

M_CAP

Benign

0.020

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.57

PhyloP100

0.48

PrimateAI

Benign

0.36

PROVEAN

Benign

0.74

REVEL

Benign

0.13

Sift

Benign

0.15

Sift4G

Benign

0.57

Polyphen

0.82

Vest4

0.13

MutPred

0.56

Loss of stability (P = 0.055)

MVP

0.88

MPC

0.63

ClinPred

0.22

GERP RS

-0.88

Varity_R

0.21

gMVP

0.80

Mutation Taster

=77/23

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over