X-70449787-C-A

Variant names:

• chrX-70449787-C-A
• rs1213060424
• NM_021120.4:c.631C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_021120.4(DLG3):​c.631C>A​(p.Arg211Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000915 in 1,092,999 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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. R211R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: DLG3 NM_021120.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP7: Synonymous conserved (PhyloP=1.6 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.631C>A	p.Arg211Arg	synonymous	Exon 4 of 19	NP_066943.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG3	ENST00000374360.8	TSL:1 MANE Select	c.631C>A	p.Arg211Arg	synonymous	Exon 4 of 19	ENSP00000363480.3
	DLG3	ENST00000194900.8	TSL:5	c.685C>A	p.Arg229Arg	synonymous	Exon 5 of 21	ENSP00000194900.4
	DLG3	ENST00000463252.5	TSL:5	n.697C>A		non_coding_transcript_exon	Exon 4 of 19

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00 AC: 0 AN: 169030 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.15e-7 AC: 1 AN: 1092999 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 359205

African (AFR) AF: 0.00 AC: 0 AN: 26367

American (AMR) AF: 0.0000291 AC: 1 AN: 34421

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19245

East Asian (EAS) AF: 0.00 AC: 0 AN: 30038

South Asian (SAS) AF: 0.00 AC: 0 AN: 53019

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4040

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 840053

Other (OTH) AF: 0.00 AC: 0 AN: 45866

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	14
DANN	Benign	0.85
PhyloP100		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs1213060424; hg19: chrX-69669637;