X-154477925-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006014.5(LAGE3):c.*19G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,184,933 control chromosomes in the GnomAD database, including 10,661 homozygotes. There are 56,667 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 2495 hom., 6896 hem., cov: 24)

Exomes 𝑓: 0.13 ( 8166 hom. 49771 hem. )

Consequence

LAGE3
NM_006014.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.989

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-154477925-C-G is Benign according to our data. Variant chrX-154477925-C-G is described in ClinVar as [Benign]. Clinvar id is 1235001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAGE3	NM_006014.5 link	c.*19G>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000357360.5	NP_006005.2	Q14657
PLXNA3	NM_017514.5 link	c.*5240C>G		downstream_gene_variant		ENST00000369682.4	NP_059984.3	P51805

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAGE3	ENST00000357360 link	c.*19G>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_006014.5	ENSP00000349923.4		Q14657
PLXNA3	ENST00000369682.4 link	c.*5240C>G		downstream_gene_variant		1	NM_017514.5	ENSP00000358696.3		P51805

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

23011

AN:

112171

Hom.:

2497

Cov.:

AF XY:

0.200

AC XY:

6882

AN XY:

34365

show subpopulations

Gnomad AFR

AF:

0.419

Gnomad AMI

AF:

0.0718

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.447

Gnomad FIN

AF:

0.0727

Gnomad MID

AF:

0.268

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.209

GnomAD3 exomes

AF:

0.163

AC:

29335

AN:

180373

Hom.:

2213

AF XY:

0.177

AC XY:

11537

AN XY:

65307

show subpopulations

Gnomad AFR exome

AF:

0.433

Gnomad AMR exome

AF:

0.0631

Gnomad ASJ exome

AF:

0.203

Gnomad EAS exome

AF:

0.145

Gnomad SAS exome

AF:

0.422

Gnomad FIN exome

AF:

0.0776

Gnomad NFE exome

AF:

0.108

Gnomad OTH exome

AF:

0.153

GnomAD4 exome

AF:

0.130

AC:

139892

AN:

1072709

Hom.:

8166

Cov.:

AF XY:

0.146

AC XY:

49771

AN XY:

341287

show subpopulations

Gnomad4 AFR exome

AF:

0.426

Gnomad4 AMR exome

AF:

0.0692

Gnomad4 ASJ exome

AF:

0.209

Gnomad4 EAS exome

AF:

0.0969

Gnomad4 SAS exome

AF:

0.432

Gnomad4 FIN exome

AF:

0.0821

Gnomad4 NFE exome

AF:

0.103

Gnomad4 OTH exome

AF:

0.166

GnomAD4 genome

AF:

0.205

AC:

23018

AN:

112224

Hom.:

2495

Cov.:

AF XY:

0.200

AC XY:

6896

AN XY:

34428

show subpopulations

Gnomad4 AFR

AF:

0.419

Gnomad4 AMR

AF:

0.117

Gnomad4 ASJ

AF:

0.199

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.446

Gnomad4 FIN

AF:

0.0727

Gnomad4 NFE

AF:

0.108

Gnomad4 OTH

AF:

0.206

Alfa

AF:

0.163

Hom.:

1539

Bravo

AF:

0.211

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Galloway-Mowat syndrome 2, X-linked

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.69

DANN

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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