X-70445294-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_021120.4(DLG3):c.93C>T(p.Gly31=) 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 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.06

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]

ACMG classification

Verdict is Benign. Variant got -11 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]. Clinvar id is 746464.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.06 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLG3	NM_021120.4	c.93C>T	p.Gly31=	synonymous_variant	1/19	ENST00000374360.8
DLG3	XM_006724625.3	c.93C>T	p.Gly31=	synonymous_variant	1/20
DLG3	XM_011530883.2	c.93C>T	p.Gly31=	synonymous_variant	1/19
DLG3	XM_006724626.3	c.93C>T	p.Gly31=	synonymous_variant	1/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLG3	ENST00000374360.8	c.93C>T	p.Gly31=	synonymous_variant	1/19	1	NM_021120.4
DLG3	ENST00000194900.8	c.93C>T	p.Gly31=	synonymous_variant	1/21	5		P1
DLG3	ENST00000463252.5	n.159C>T		non_coding_transcript_exon_variant	1/19	5

Frequencies

GnomAD3 genomes AF: 0.000185 AC: 21 AN: 113344 Hom.: 0 Cov.: 24 AF XY: 0.000197 AC XY: 7 AN XY: 35488

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

GnomAD3 exomes AF: 0.000394 AC: 40 AN: 101405 Hom.: 0 AF XY: 0.000249 AC XY: 9 AN XY: 36217

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 SAS 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.: 0 Cov.: 31 AF XY: 0.000102 AC XY: 35 AN XY: 343130

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00483

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000171

Gnomad4 OTH exome AF: 0.000361

GnomAD4 genome AF: 0.000185 AC: 21 AN: 113344 Hom.: 0 Cov.: 24 AF XY: 0.000197 AC XY: 7 AN XY: 35488

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00715

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.000650

Alfa AF: 0.000825 Hom.: 5

Bravo AF: 0.000181

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	11
Dann	Benign	0.81

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

LitVar

Other links and lift over

dbSNP: rs776667412; hg19: chrX-69665144;