1-34900163-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001080418.3(DLGAP3):c.1218C>T(p.Ser406=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000774 in 1,613,976 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0010 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00075 (8 hom.)
• Consequence: DLGAP3 NM_001080418.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0210

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 Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 1-34900163-G-A is Benign according to our data. Variant chr1-34900163-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 724007.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.021 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLGAP3	NM_001080418.3	c.1218C>T	p.Ser406=	synonymous_variant	4/12	ENST00000373347.6
DLGAP3	XM_011541879.3	c.1218C>T	p.Ser406=	synonymous_variant	5/13
DLGAP3	XM_047426631.1	c.1218C>T	p.Ser406=	synonymous_variant	4/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLGAP3	ENST00000373347.6	c.1218C>T	p.Ser406=	synonymous_variant	4/12	5	NM_001080418.3	P1
DLGAP3	ENST00000235180.4	c.1218C>T	p.Ser406=	synonymous_variant	2/10	2		P1

Frequencies

GnomAD3 genomes AF: 0.00101 AC: 154 AN: 152172 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.0354

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.00133 AC: 334 AN: 251350 Hom.: 3 AF XY: 0.00133 AC XY: 181 AN XY: 135860

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.0263

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000440

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000749 AC: 1095 AN: 1461686 Hom.: 8 Cov.: 32 AF XY: 0.000773 AC XY: 562 AN XY: 727152

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.000291

Gnomad4 ASJ exome AF: 0.0272

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000218

Gnomad4 OTH exome AF: 0.00205

GnomAD4 genome AF: 0.00101 AC: 154 AN: 152290 Hom.: 1 Cov.: 32 AF XY: 0.000953 AC XY: 71 AN XY: 74466

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.0354

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00262 Hom.: 0

Bravo AF: 0.00102

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.00113

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Nov 16, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	DLGAP3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	3.8
Dann	Benign	0.85

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: rs150566254; hg19: chr1-35365764; COSMIC: COSV52393755;