X-70453961-T-C

Position:

• chrX-70453961-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_021120.4(DLG3):​c.1302+168T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (13044 hom., 18220 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: DLG3 NM_021120.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.783

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]

DLG3-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant X-70453961-T-C is Benign according to our data. Variant chrX-70453961-T-C is described in ClinVar as [Benign]. Clinvar id is 1257232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG3	NM_021120.4	c.1302+168T>C		intron_variant		ENST00000374360.8	NP_066943.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLG3	ENST00000374360.8	c.1302+168T>C		intron_variant		1	NM_021120.4	ENSP00000363480.3

Frequencies

GnomAD3 genomes AF: 0.557 AC: 61745 AN: 110809 Hom.: 13029 Cov.: 23 AF XY: 0.550 AC XY: 18172 AN XY: 33025

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.464

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.579

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.557 AC: 61805 AN: 110863 Hom.: 13044 Cov.: 23 AF XY: 0.551 AC XY: 18220 AN XY: 33089

Gnomad4 AFR AF: 0.782

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.584

Alfa AF: 0.475 Hom.: 13236

Bravo AF: 0.580

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs2274309; hg19: chrX-69673811;