dbSNP rs1213060424: DLG3:p.Arg211Arg (chrX-70449787-C-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.60

Publications

1 publications found

Variant links:

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

DLG3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
DLG3	NM_021120.4 link	c.631C>A	p.Arg211Arg	synonymous_variant	Exon 4 of 19	ENST00000374360.8	NP_066943.2
DLG3	XM_006724625.3 link	c.631C>A	p.Arg211Arg	synonymous_variant	Exon 4 of 20		XP_006724688.1
DLG3	XM_011530883.2 link	c.631C>A	p.Arg211Arg	synonymous_variant	Exon 4 of 19		XP_011529185.1
DLG3	XM_006724626.3 link	c.631C>A	p.Arg211Arg	synonymous_variant	Exon 4 of 20		XP_006724689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
DLG3	ENST00000374360.8 link	c.631C>A	p.Arg211Arg	synonymous_variant	Exon 4 of 19	1	NM_021120.4	ENSP00000363480.3
DLG3	ENST00000194900.8 link	c.685C>A	p.Arg229Arg	synonymous_variant	Exon 5 of 21	5		ENSP00000194900.4
DLG3	ENST00000463252.5 link	n.697C>A		non_coding_transcript_exon_variant	Exon 4 of 19	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

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:

AN:

1092999

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

359205

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26367

American (AMR)

AF:

0.0000291

AC:

AN:

34421

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19245

East Asian (EAS)

AF:

0.00

AC:

AN:

30038

South Asian (SAS)

AF:

0.00

AC:

AN:

53019

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4040

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

840053

Other (OTH)

AF:

0.00

AC:

AN:

45866

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over