X-70454052-T-G

Variant names:

• chrX-70454052-T-G
• rs2274310
• NM_021120.4:c.1303-162T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 -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 VariationId 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.

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.1303-162T>G		intron	N/A	NP_066943.2	Q92796-1
	DLG3	NM_020730.3		c.292-162T>G		intron	N/A	NP_065781.1	Q92796-2
	DLG3-AS1	NR_046586.1		n.84-746A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG3	ENST00000374360.8	TSL:1 MANE Select	c.1303-162T>G		intron	N/A	ENSP00000363480.3	Q92796-1
	DLG3	ENST00000374355.8	TSL:1	c.292-162T>G		intron	N/A	ENSP00000363475.3	Q92796-2
	DLG3	ENST00000194900.8	TSL:5	c.1357-162T>G		intron	N/A	ENSP00000194900.4	Q5JUW8

Frequencies

GnomAD3 genomes AF: 0.0582 AC: 6509 AN: 111893 Hom.: 198 Cov.: 23

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

African (AFR) AF: 0.0467 AC: 1439 AN: 30845

American (AMR) AF: 0.0461 AC: 491 AN: 10646

Ashkenazi Jewish (ASJ) AF: 0.0560 AC: 148 AN: 2642

East Asian (EAS) AF: 0.241 AC: 845 AN: 3503

South Asian (SAS) AF: 0.153 AC: 406 AN: 2648

European-Finnish (FIN) AF: 0.0637 AC: 389 AN: 6102

Middle Eastern (MID) AF: 0.0321 AC: 7 AN: 218

European-Non Finnish (NFE) AF: 0.0500 AC: 2659 AN: 53152

Other (OTH) AF: 0.0645 AC: 98 AN: 1519

Alfa AF: 0.0547 Hom.: 1611

Bravo AF: 0.0566

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.3
DANN	Benign	0.75
PhyloP100		0.089
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2274310; hg19: chrX-69673902;