Genetic Variant NM_021120.4:c.152A>G (chrX-70445353-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_021120.4(DLG3):c.152A>G(p.Tyr51Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000884 in 113,147 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.

Frequency

Genomes: 𝑓 0.0000088 ( 0 hom., 0 hem., cov: 24)

Consequence

DLG3
NM_021120.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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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=0.39622405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG3	NM_021120.4 link	c.152A>G	p.Tyr51Cys	missense_variant	Exon 1 of 19	ENST00000374360.8	NP_066943.2	Q92796-1Q59FY1
DLG3	XM_006724625.3 link	c.152A>G	p.Tyr51Cys	missense_variant	Exon 1 of 20		XP_006724688.1
DLG3	XM_011530883.2 link	c.152A>G	p.Tyr51Cys	missense_variant	Exon 1 of 19		XP_011529185.1
DLG3	XM_006724626.3 link	c.152A>G	p.Tyr51Cys	missense_variant	Exon 1 of 20		XP_006724689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DLG3	ENST00000374360.8 link	c.152A>G	p.Tyr51Cys	missense_variant	Exon 1 of 19	1	NM_021120.4	ENSP00000363480.3	Q92796-1
DLG3	ENST00000194900.8 link	c.152A>G	p.Tyr51Cys	missense_variant	Exon 1 of 21	5		ENSP00000194900.4	Q5JUW8
DLG3	ENST00000463252.5 link	n.218A>G		non_coding_transcript_exon_variant	Exon 1 of 19	5

Frequencies

GnomAD3 genomes

AF:

0.00000884

AC:

AN:

113147

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35317

show subpopulations

Gnomad AFR

AF:

0.0000320

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000884

AC:

AN:

113147

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35317

show subpopulations

Gnomad4 AFR

AF:

0.0000320

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.075

T;T

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.93

D;D

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.40

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.69

.;N

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.95

N;N

REVEL

Uncertain

0.35

Sift

Benign

0.043

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

0.93

.;P

Vest4

0.43

MutPred

0.68

Loss of phosphorylation at Y51 (P = 0.0153);Loss of phosphorylation at Y51 (P = 0.0153);

MVP

0.86

MPC

1.5

ClinPred

0.70

GERP RS

3.7

Varity_R

0.28

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over