X-70445258-G-C

Variant names:

• chrX-70445258-G-C
• NM_021120.4:c.57G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021120.4(DLG3):​c.57G>C​(p.Leu19Leu) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: DLG3 NM_021120.4 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.68

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG3	NM_021120.4	c.57G>C	p.Leu19Leu	synonymous_variant	Exon 1 of 19	ENST00000374360.8	NP_066943.2
DLG3	XM_006724625.3	c.57G>C	p.Leu19Leu	synonymous_variant	Exon 1 of 20		XP_006724688.1
DLG3	XM_011530883.2	c.57G>C	p.Leu19Leu	synonymous_variant	Exon 1 of 19		XP_011529185.1
DLG3	XM_006724626.3	c.57G>C	p.Leu19Leu	synonymous_variant	Exon 1 of 20		XP_006724689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG3	ENST00000374360.8	c.57G>C	p.Leu19Leu	synonymous_variant	Exon 1 of 19	1	NM_021120.4	ENSP00000363480.3
DLG3	ENST00000194900.8	c.57G>C	p.Leu19Leu	synonymous_variant	Exon 1 of 21	5		ENSP00000194900.4
DLG3	ENST00000463252.5	n.123G>C		non_coding_transcript_exon_variant	Exon 1 of 19	5

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, X-linked 90 Uncertain:1

Jun 14, 2024

Department of Human Genetics, Hannover Medical School

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	11
DANN	Benign	0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-69665108;