X-154477925-C-G

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

2

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]
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]

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
LAGE3NM_006014.5 linkc.*19G>C 3_prime_UTR_variant Exon 3 of 3 ENST00000357360.5 NP_006005.2 Q14657
PLXNA3NM_017514.5 linkc.*5240C>G downstream_gene_variant ENST00000369682.4 NP_059984.3 P51805

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LAGE3ENST00000357360 linkc.*19G>C 3_prime_UTR_variant Exon 3 of 3 1 NM_006014.5 ENSP00000349923.4 Q14657
PLXNA3ENST00000369682.4 linkc.*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.:
24
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.:
26
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.:
24
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.

Other links and lift over

dbSNP: rs6567; hg19: chrX-153706264; COSMIC: COSV62074270; COSMIC: COSV62074270; API