Variant X-154478313-T-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 NM_006014.5(LAGE3):c.287A>T(p.Asp96Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,209,551 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

LAGE3
NM_006014.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.14

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:

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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=0.21131247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAGE3	NM_006014.5 linkuse as main transcript	c.287A>T	p.Asp96Val	missense_variant	2/3	ENST00000357360.5	NP_006005.2	Q14657

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAGE3	ENST00000357360.5 linkuse as main transcript	c.287A>T	p.Asp96Val	missense_variant	2/3	1	NM_006014.5	ENSP00000349923.4		Q14657

Frequencies

GnomAD3 genomes

AF:

0.00000893

AC:

AN:

111989

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34167

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:

0.000281

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:

0.0000110

AC:

AN:

182325

Hom.:

AF XY:

0.00

AC XY:

AN XY:

66835

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000726

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000182

AC:

AN:

1097510

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363018

show subpopulations

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:

0.00000238

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000893

AC:

AN:

112041

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34229

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000282

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Galloway-Mowat syndrome 2, X-linked

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

New York Genome Center

Jun 19, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.066

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.70

M_CAP

Benign

0.041

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.13

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.032

Polyphen

0.40

Vest4

0.32

MVP

0.45

MPC

0.41

ClinPred

0.39

GERP RS

4.1

Varity_R

0.51

gMVP

0.68

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

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