X-154478058-GA-CG

Variant names:

• chrX-154478058-GC-CG
• NM_006014.5:c.318-1_318delGCinsCG
• LAGE3 p.107

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP7

The NM_006014.5(LAGE3):​c.318-1_318delGCinsCG​(p.107) variant causes a splice acceptor, splice region, synonymous, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 24)
• Consequence: LAGE3 NM_006014.5 splice_acceptor, splice_region, synonymous, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.26
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Galloway-Mowat syndrome 2, X-linked

  Inheritance: XL Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Galloway-Mowat syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP7: Synonymous conserved (PhyloP=3.26 with no splicing effect.

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.318-1_318delGCinsCG	p.107	splice_acceptor splice_region synonymous intron	N/A	NP_006005.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAGE3	ENST00000357360.5	TSL:1 MANE Select	c.318-1_318delGCinsCG	p.107	splice_acceptor splice_region synonymous intron	N/A	ENSP00000349923.4	Q14657

Frequencies

GnomAD3 genomes Cov.: 24

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-153706397;