X-70445326-G-GT

Variant names:

• chrX-70445326-G-GT
• rs2086554538
• NM_021120.4:c.126dupT

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_021120.4(DLG3):​c.126dupT​(p.Gly43TrpfsTer46) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 24)
• Consequence: DLG3 NM_021120.4 frameshift
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.0230

Genes affected

DLG3 (HGNC:2902): (discs large MAGUK scaffold protein 3) This gene encodes a member of the membrane-associated guanylate kinase protein family. The encoded protein may play a role in clustering of NMDA receptors at excitatory synapses. It may also negatively regulate cell proliferation through interaction with the C-terminal region of the adenomatosis polyposis coli tumor suppressor protein. Mutations in this gene have been associated with X-linked cognitive disability. Alternatively spliced transcript variants have been described. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG3	NM_021120.4	c.126dupT	p.Gly43TrpfsTer46	frameshift_variant	Exon 1 of 19	ENST00000374360.8	NP_066943.2
DLG3	XM_006724625.3	c.126dupT	p.Gly43TrpfsTer46	frameshift_variant	Exon 1 of 20		XP_006724688.1
DLG3	XM_011530883.2	c.126dupT	p.Gly43TrpfsTer46	frameshift_variant	Exon 1 of 19		XP_011529185.1
DLG3	XM_006724626.3	c.126dupT	p.Gly43TrpfsTer46	frameshift_variant	Exon 1 of 20		XP_006724689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG3	ENST00000374360.8	c.126dupT	p.Gly43TrpfsTer46	frameshift_variant	Exon 1 of 19	1	NM_021120.4	ENSP00000363480.3
DLG3	ENST00000194900.8	c.126dupT	p.Gly43TrpfsTer46	frameshift_variant	Exon 1 of 21	5		ENSP00000194900.4
DLG3	ENST00000463252.5	n.192dupT		non_coding_transcript_exon_variant	Exon 1 of 19	5

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

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GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

Variant interpretted as Likely pathogenic and reported on 09-18-2019 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs2086554538; hg19: chrX-69665176;