rs2274309

Variant names:

• chrX-70453961-T-C
• rs2274309
• NM_021120.4:c.1302+168T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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:40182): (DLG3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 1257232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021120.4. 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
	DLG3	NM_021120.4	MANE Select	c.1302+168T>C		intron	N/A	NP_066943.2	Q92796-1
	DLG3	NM_020730.3		c.291+168T>C		intron	N/A	NP_065781.1	Q92796-2
	DLG3-AS1	NR_046586.1		n.84-655A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG3	ENST00000374360.8	TSL:1 MANE Select	c.1302+168T>C		intron	N/A	ENSP00000363480.3	Q92796-1
	DLG3	ENST00000374355.8	TSL:1	c.291+168T>C		intron	N/A	ENSP00000363475.3	Q92796-2
	DLG3	ENST00000194900.8	TSL:5	c.1356+168T>C		intron	N/A	ENSP00000194900.4	Q5JUW8

Frequencies

GnomAD3 genomes AF: 0.557 AC: 61745 AN: 110809 Hom.: 13029 Cov.: 23

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

African (AFR) AF: 0.782 AC: 23814 AN: 30470

American (AMR) AF: 0.604 AC: 6338 AN: 10499

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 1333 AN: 2636

East Asian (EAS) AF: 0.384 AC: 1346 AN: 3505

South Asian (SAS) AF: 0.520 AC: 1358 AN: 2613

European-Finnish (FIN) AF: 0.481 AC: 2851 AN: 5932

Middle Eastern (MID) AF: 0.440 AC: 95 AN: 216

European-Non Finnish (NFE) AF: 0.444 AC: 23450 AN: 52813

Other (OTH) AF: 0.584 AC: 884 AN: 1514

Alfa AF: 0.493 Hom.: 19921

Bravo AF: 0.580

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.66
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2274309; hg19: chrX-69673811;