NM_021120.4:c.126T>C

Variant names:

• chrX-70445327-T-C
• rs982660834
• NM_021120.4:c.126T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_021120.4(DLG3):​c.126T>C​(p.Gly42Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000949 in 1,053,774 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G42G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.5e-7 (0 hom. 1 hem.)
• Consequence: DLG3 NM_021120.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• 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 Gene-Disease associations (from GenCC):

• intellectual disability, X-linked 90

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=0.023 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG3	NM_021120.4	MANE Select	c.126T>C	p.Gly42Gly	synonymous	Exon 1 of 19	NP_066943.2	Q92796-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG3	ENST00000374360.8	TSL:1 MANE Select	c.126T>C	p.Gly42Gly	synonymous	Exon 1 of 19	ENSP00000363480.3	Q92796-1
	DLG3	ENST00000194900.8	TSL:5	c.126T>C	p.Gly42Gly	synonymous	Exon 1 of 21	ENSP00000194900.4	Q5JUW8
	DLG3	ENST00000949779.1		c.126T>C	p.Gly42Gly	synonymous	Exon 1 of 20	ENSP00000619838.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.00000957 AC: 1 AN: 104496 AF XY: 0.0000277

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: 0.0000258

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.49e-7 AC: 1 AN: 1053774 Hom.: 0 Cov.: 31 AF XY: 0.00000291 AC XY: 1 AN XY: 343578

African (AFR) AF: 0.00 AC: 0 AN: 25183

American (AMR) AF: 0.00 AC: 0 AN: 28674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18636

East Asian (EAS) AF: 0.00 AC: 0 AN: 27570

South Asian (SAS) AF: 0.00 AC: 0 AN: 50120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33551

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3945

European-Non Finnish (NFE) AF: 0.00000122 AC: 1 AN: 821634

Other (OTH) AF: 0.00 AC: 0 AN: 44461

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.53
PhyloP100		0.023
PromoterAI		0.14	Neutral
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: rs982660834; hg19: chrX-69665177;