rs11587343

chr1-34868849-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001080418.3(DLGAP3):c.2241C>T(p.Tyr747=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,586,072 control chromosomes in the GnomAD database, including 10 homozygotes. 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 0.0019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (10 hom.)
• Consequence: DLGAP3 NM_001080418.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

Genes affected

DLGAP3 (HGNC:30368): (DLG associated protein 3) Predicted to enable PDZ domain binding activity; molecular adaptor activity; and scaffold protein binding activity. Predicted to be involved in protein-containing complex assembly and regulation of postsynaptic neurotransmitter receptor activity. Predicted to be located in synapse. Predicted to be part of postsynaptic density. Predicted to be active in several cellular components, including cholinergic synapse; glutamatergic synapse; and neuromuscular junction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=-1.1 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLGAP3	NM_001080418.3	c.2241C>T	p.Tyr747=	synonymous_variant	9/12	ENST00000373347.6
DLGAP3	XM_011541879.3	c.2241C>T	p.Tyr747=	synonymous_variant	10/13
DLGAP3	XM_047426631.1	c.2241C>T	p.Tyr747=	synonymous_variant	9/12
DLGAP3	XM_011541880.3	c.750C>T	p.Tyr250=	synonymous_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLGAP3	ENST00000373347.6	c.2241C>T	p.Tyr747=	synonymous_variant	9/12	5	NM_001080418.3	P1
DLGAP3	ENST00000235180.4	c.2241C>T	p.Tyr747=	synonymous_variant	7/10	2		P1

Frequencies

GnomAD3 genomes AF: 0.00188 AC: 286 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00368

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00183 AC: 387 AN: 211766 Hom.: 0 AF XY: 0.00179 AC XY: 212 AN XY: 118468

Gnomad AFR exome AF: 0.000806

Gnomad AMR exome AF: 0.000122

Gnomad ASJ exome AF: 0.000112

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000277

Gnomad FIN exome AF: 0.0000877

Gnomad NFE exome AF: 0.00369

Gnomad OTH exome AF: 0.00225

GnomAD4 exome AF: 0.00305 AC: 4372 AN: 1433780 Hom.: 10 Cov.: 32 AF XY: 0.00296 AC XY: 2108 AN XY: 711682

Gnomad4 AFR exome AF: 0.000514

Gnomad4 AMR exome AF: 0.000184

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.000153

Gnomad4 FIN exome AF: 0.000356

Gnomad4 NFE exome AF: 0.00381

Gnomad4 OTH exome AF: 0.00184

GnomAD4 genome AF: 0.00188 AC: 287 AN: 152292 Hom.: 0 Cov.: 32 AF XY: 0.00181 AC XY: 135 AN XY: 74464

Gnomad4 AFR AF: 0.000673

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00368

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00204 Hom.: 0

Bravo AF: 0.00169

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	0.44
Dann	Benign	0.71

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

Other links and lift over

dbSNP: rs11587343; hg19: chr1-35334450; COSMIC: COSV99333228;