X-70454052-T-G

Position:

• chrX-70454052-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021120.4(DLG3):​c.1303-162T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0584 in 111,948 control chromosomes in the GnomAD database, including 202 homozygotes. There are 2,015 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.058 (202 hom., 2015 hem., cov: 23)
• Consequence: DLG3 NM_021120.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0890

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant X-70454052-T-G is Benign according to our data. Variant chrX-70454052-T-G is described in ClinVar as [Benign]. Clinvar id is 1265795.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG3	NM_021120.4	c.1303-162T>G		intron_variant		ENST00000374360.8	NP_066943.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLG3	ENST00000374360.8	c.1303-162T>G		intron_variant		1	NM_021120.4	ENSP00000363480.3

Frequencies

GnomAD3 genomes AF: 0.0582 AC: 6509 AN: 111893 Hom.: 198 Cov.: 23 AF XY: 0.0586 AC XY: 1997 AN XY: 34081

Gnomad AFR AF: 0.0461

Gnomad AMI AF: 0.0788

Gnomad AMR AF: 0.0462

Gnomad ASJ AF: 0.0560

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.0637

Gnomad MID AF: 0.0335

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.0573

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

GnomAD4 genome AF: 0.0584 AC: 6535 AN: 111948 Hom.: 202 Cov.: 23 AF XY: 0.0590 AC XY: 2015 AN XY: 34146

Gnomad4 AFR AF: 0.0467

Gnomad4 AMR AF: 0.0461

Gnomad4 ASJ AF: 0.0560

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.0637

Gnomad4 NFE AF: 0.0500

Gnomad4 OTH AF: 0.0645

Alfa AF: 0.0581 Hom.: 992

Bravo AF: 0.0566

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.3
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2274310; hg19: chrX-69673902;