Genetic Variant NM_021120.4:c.93C>T (chrX-70445294-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_021120.4(DLG3):c.93C>T(p.Gly31Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,164,164 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 42 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 0.00019 ( 0 hom., 7 hem., cov: 24)

Exomes 𝑓: 0.00011 ( 0 hom. 35 hem. )

Consequence

DLG3
NM_021120.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.06

Publications

0 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: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant X-70445294-C-T is Benign according to our data. Variant chrX-70445294-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 746464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.06 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 7 XL gene

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.93C>T	p.Gly31Gly	synonymous	Exon 1 of 19	NP_066943.2	Q92796-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DLG3	ENST00000374360.8	TSL:1 MANE Select	c.93C>T	p.Gly31Gly	synonymous	Exon 1 of 19	ENSP00000363480.3	Q92796-1
DLG3	ENST00000194900.8	TSL:5	c.93C>T	p.Gly31Gly	synonymous	Exon 1 of 21	ENSP00000194900.4	Q5JUW8
DLG3	ENST00000949779.1		c.93C>T	p.Gly31Gly	synonymous	Exon 1 of 20	ENSP00000619838.1

Frequencies

GnomAD3 genomes

AF:

0.000185

AC:

AN:

113344

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00715

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.000650

GnomAD2 exomes

AF:

0.000394

AC:

AN:

101405

AF XY:

0.000249

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00582

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000109

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000114

AC:

120

AN:

1050820

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

343130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25023

American (AMR)

AF:

0.00

AC:

AN:

28040

Ashkenazi Jewish (ASJ)

AF:

0.00483

AC:

AN:

18620

East Asian (EAS)

AF:

0.00

AC:

AN:

27286

South Asian (SAS)

AF:

0.00

AC:

AN:

49928

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33804

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3887

European-Non Finnish (NFE)

AF:

0.0000171

AC:

AN:

819871

Other (OTH)

AF:

0.000361

AC:

AN:

44361

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000185

AC:

AN:

113344

Hom.:

Cov.:

AF XY:

0.000197

AC XY:

AN XY:

35488

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31330

American (AMR)

AF:

0.00

AC:

AN:

10875

Ashkenazi Jewish (ASJ)

AF:

0.00715

AC:

AN:

2656

East Asian (EAS)

AF:

0.00

AC:

AN:

3566

South Asian (SAS)

AF:

0.00

AC:

AN:

2845

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6319

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53294

Other (OTH)

AF:

0.000650

AC:

AN:

1539

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000825

Hom.:

Bravo

AF:

0.000181

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

1.1

PromoterAI

0.0050

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over