NM_001080418.3:c.2379C>T

Variant names:

• chr1-34868711-G-A
• rs77048244
• NM_001080418.3:c.2379C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001080418.3(DLGAP3):​c.2379C>T​(p.Arg793Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00067 in 1,610,906 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0033 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (4 hom.)
• Consequence: DLGAP3 NM_001080418.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.102
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 1-34868711-G-A is Benign according to our data. Variant chr1-34868711-G-A is described in ClinVar as [Benign]. Clinvar id is 716659.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.102 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP3	NM_001080418.3	c.2379C>T	p.Arg793Arg	synonymous_variant	Exon 9 of 12	ENST00000373347.6	NP_001073887.1
DLGAP3	XM_011541879.3	c.2379C>T	p.Arg793Arg	synonymous_variant	Exon 10 of 13		XP_011540181.1
DLGAP3	XM_047426631.1	c.2379C>T	p.Arg793Arg	synonymous_variant	Exon 9 of 12		XP_047282587.1
DLGAP3	XM_011541880.3	c.888C>T	p.Arg296Arg	synonymous_variant	Exon 5 of 8		XP_011540182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP3	ENST00000373347.6	c.2379C>T	p.Arg793Arg	synonymous_variant	Exon 9 of 12	5	NM_001080418.3	ENSP00000362444.1
DLGAP3	ENST00000235180.4	c.2379C>T	p.Arg793Arg	synonymous_variant	Exon 7 of 10	2		ENSP00000235180.4

Frequencies

GnomAD3 genomes AF: 0.00334 AC: 508 AN: 152220 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

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: 0.0000735

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.000861 AC: 213 AN: 247498 AF XY: 0.000617

Gnomad AFR exome AF: 0.0113

Gnomad AMR exome AF: 0.000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000518

Gnomad NFE exome AF: 0.0000711

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.000393 AC: 573 AN: 1458570 Hom.: 4 Cov.: 32 AF XY: 0.000322 AC XY: 234 AN XY: 725830

African (AFR) AF: 0.0126 AC: 421 AN: 33480

American (AMR) AF: 0.000581 AC: 26 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86256

European-Finnish (FIN) AF: 0.0000199 AC: 1 AN: 50182

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000522 AC: 58 AN: 1111960

Other (OTH) AF: 0.000828 AC: 50 AN: 60372

GnomAD4 genome AF: 0.00332 AC: 506 AN: 152336 Hom.: 1 Cov.: 32 AF XY: 0.00336 AC XY: 250 AN XY: 74504

African (AFR) AF: 0.0114 AC: 476 AN: 41574

American (AMR) AF: 0.00118 AC: 18 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68024

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00196 Hom.: 0

Bravo AF: 0.00382

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 19, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	15
DANN	Benign	0.81
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs77048244; hg19: chr1-35334312;