Variant X-70445353-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_021120.4(DLG3):c.152A>C(p.Tyr51Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000283 in 1,059,209 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000028 ( 0 hom. 1 hem. )

Consequence

DLG3
NM_021120.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.61

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 links:

DLG3 (HGNC:):

DLG3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40833414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG3	NM_021120.4 linkuse as main transcript	c.152A>C	p.Tyr51Ser	missense_variant	1/19	ENST00000374360.8	NP_066943.2	Q92796-1Q59FY1
DLG3	XM_006724625.3 linkuse as main transcript	c.152A>C	p.Tyr51Ser	missense_variant	1/20		XP_006724688.1
DLG3	XM_011530883.2 linkuse as main transcript	c.152A>C	p.Tyr51Ser	missense_variant	1/19		XP_011529185.1
DLG3	XM_006724626.3 linkuse as main transcript	c.152A>C	p.Tyr51Ser	missense_variant	1/20		XP_006724689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DLG3	ENST00000374360.8 linkuse as main transcript	c.152A>C	p.Tyr51Ser	missense_variant	1/19	1	NM_021120.4	ENSP00000363480.3	Q92796-1
DLG3	ENST00000194900.8 linkuse as main transcript	c.152A>C	p.Tyr51Ser	missense_variant	1/21	5		ENSP00000194900.4	Q5JUW8
DLG3	ENST00000463252.5 linkuse as main transcript	n.218A>C		non_coding_transcript_exon_variant	1/19	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000899

AC:

AN:

111250

Hom.:

AF XY:

0.00

AC XY:

AN XY:

36712

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000481

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000283

AC:

AN:

1059209

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

345049

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000102

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000183

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.152A>C (p.Y51S) alteration is located in exon 1 (coding exon 1) of the DLG3 gene. This alteration results from a A to C substitution at nucleotide position 152, causing the tyrosine (Y) at amino acid position 51 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.061

T;T

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.87

D;D

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.41

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

.;N

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.48

N;N

REVEL

Benign

0.29

Sift

Benign

0.22

T;T

Sift4G

Pathogenic

0.0010

D;D

Polyphen

0.14

.;B

Vest4

0.50

MutPred

0.65

Gain of glycosylation at Y51 (P = 2e-04);Gain of glycosylation at Y51 (P = 2e-04);

MVP

0.94

MPC

1.0

ClinPred

0.50

GERP RS

3.7

Varity_R

0.32

gMVP

0.70

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over