NM_021120.4:c.1281C>T

Variant names:

• chrX-70453772-C-T
• rs1473465948
• NM_021120.4:c.1281C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_021120.4(DLG3):​c.1281C>T​(p.Arg427Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000418 in 1,197,474 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.0000028 (0 hom. 1 hem.)
• Consequence: DLG3 NM_021120.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.41
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant X-70453772-C-T is Benign according to our data. Variant chrX-70453772-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 434946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.41 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG3	NM_021120.4	MANE Select	c.1281C>T	p.Arg427Arg	synonymous	Exon 8 of 19	NP_066943.2
	DLG3	NM_020730.3		c.270C>T	p.Arg90Arg	synonymous	Exon 2 of 14	NP_065781.1
	DLG3-AS1	NR_046586.1		n.84-466G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG3	ENST00000374360.8	TSL:1 MANE Select	c.1281C>T	p.Arg427Arg	synonymous	Exon 8 of 19	ENSP00000363480.3
	DLG3	ENST00000374355.8	TSL:1	c.270C>T	p.Arg90Arg	synonymous	Exon 2 of 14	ENSP00000363475.3
	DLG3	ENST00000194900.8	TSL:5	c.1335C>T	p.Arg445Arg	synonymous	Exon 9 of 21	ENSP00000194900.4

Frequencies

GnomAD3 genomes AF: 0.0000180 AC: 2 AN: 111293 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000377

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000183 AC: 3 AN: 163967 AF XY: 0.0000198

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000415

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000276 AC: 3 AN: 1086181 Hom.: 0 Cov.: 31 AF XY: 0.00000283 AC XY: 1 AN XY: 352773

African (AFR) AF: 0.00 AC: 0 AN: 26239

American (AMR) AF: 0.00 AC: 0 AN: 34232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18737

East Asian (EAS) AF: 0.00 AC: 0 AN: 30037

South Asian (SAS) AF: 0.00 AC: 0 AN: 51534

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40002

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4066

European-Non Finnish (NFE) AF: 0.00000359 AC: 3 AN: 835707

Other (OTH) AF: 0.00 AC: 0 AN: 45627

GnomAD4 genome AF: 0.0000180 AC: 2 AN: 111293 Hom.: 0 Cov.: 22 AF XY: 0.0000298 AC XY: 1 AN XY: 33505

African (AFR) AF: 0.00 AC: 0 AN: 30568

American (AMR) AF: 0.00 AC: 0 AN: 10469

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3536

South Asian (SAS) AF: 0.00 AC: 0 AN: 2593

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6013

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000377 AC: 2 AN: 53057

Other (OTH) AF: 0.00 AC: 0 AN: 1488

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Nov 09, 2015

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Jun 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DLG3: BP4, BP7

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
DANN	Benign	0.86
PhyloP100		2.4
Mutation Taster		=100/0	polymorphism

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: rs1473465948; hg19: chrX-69673622;