rs28391150

Variant names:

• chrX-70453614-C-T
• rs28391150
• NM_021120.4:c.1146-23C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021120.4(DLG3):​c.1146-23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,202,579 control chromosomes in the GnomAD database, including 14,093 homozygotes. There are 68,994 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1103 hom., 4792 hem., cov: 22)
  • Exomes 𝑓: 0.18 (12990 hom. 64202 hem.)
• Consequence: DLG3 NM_021120.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.286
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant X-70453614-C-T is Benign according to our data. Variant chrX-70453614-C-T is described in ClinVar as Benign. ClinVar VariationId is 1225363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 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.1146-23C>T		intron	N/A	NP_066943.2	Q92796-1
	DLG3	NM_020730.3		c.135-23C>T		intron	N/A	NP_065781.1	Q92796-2
	DLG3-AS1	NR_046586.1		n.84-308G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG3	ENST00000374360.8	TSL:1 MANE Select	c.1146-23C>T		intron	N/A	ENSP00000363480.3	Q92796-1
	DLG3	ENST00000374355.8	TSL:1	c.135-23C>T		intron	N/A	ENSP00000363475.3	Q92796-2
	DLG3	ENST00000194900.8	TSL:5	c.1200-23C>T		intron	N/A	ENSP00000194900.4	Q5JUW8

Frequencies

GnomAD3 genomes AF: 0.150 AC: 16671 AN: 111031 Hom.: 1108 Cov.: 22

Gnomad AFR AF: 0.0839

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.00759

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.208

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.153

GnomAD2 exomes AF: 0.146 AC: 24680 AN: 169224 AF XY: 0.143

Gnomad AFR exome AF: 0.0819

Gnomad AMR exome AF: 0.0688

Gnomad ASJ exome AF: 0.152

Gnomad EAS exome AF: 0.00509

Gnomad FIN exome AF: 0.278

Gnomad NFE exome AF: 0.187

Gnomad OTH exome AF: 0.157

GnomAD4 exome AF: 0.181 AC: 197024 AN: 1091494 Hom.: 12990 Cov.: 31 AF XY: 0.179 AC XY: 64202 AN XY: 358246

African (AFR) AF: 0.0815 AC: 2142 AN: 26282

American (AMR) AF: 0.0739 AC: 2568 AN: 34746

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 2977 AN: 19226

East Asian (EAS) AF: 0.00366 AC: 110 AN: 30078

South Asian (SAS) AF: 0.132 AC: 6999 AN: 52935

European-Finnish (FIN) AF: 0.282 AC: 11261 AN: 39997

Middle Eastern (MID) AF: 0.194 AC: 732 AN: 3766

European-Non Finnish (NFE) AF: 0.194 AC: 162353 AN: 838628

Other (OTH) AF: 0.172 AC: 7882 AN: 45836

GnomAD4 genome AF: 0.150 AC: 16668 AN: 111085 Hom.: 1103 Cov.: 22 AF XY: 0.144 AC XY: 4792 AN XY: 33297

African (AFR) AF: 0.0838 AC: 2565 AN: 30599

American (AMR) AF: 0.115 AC: 1210 AN: 10482

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 425 AN: 2640

East Asian (EAS) AF: 0.00761 AC: 27 AN: 3546

South Asian (SAS) AF: 0.114 AC: 295 AN: 2597

European-Finnish (FIN) AF: 0.280 AC: 1655 AN: 5921

Middle Eastern (MID) AF: 0.174 AC: 38 AN: 219

European-Non Finnish (NFE) AF: 0.191 AC: 10104 AN: 52889

Other (OTH) AF: 0.157 AC: 237 AN: 1513

Alfa AF: 0.169 Hom.: 1449

Bravo AF: 0.138

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	-0.82
CADD	Benign	8.3
DANN	Benign	0.65
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs28391150; hg19: chrX-69673464;