1-34868711-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001080418.3(DLGAP3):​c.2379C>A​(p.Arg793Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R793R) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DLGAP3 NM_001080418.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=0.102 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP3	NM_001080418.3	c.2379C>A	p.Arg793Arg	synonymous_variant	Exon 9 of 12	ENST00000373347.6	NP_001073887.1
DLGAP3	XM_011541879.3	c.2379C>A	p.Arg793Arg	synonymous_variant	Exon 10 of 13		XP_011540181.1
DLGAP3	XM_047426631.1	c.2379C>A	p.Arg793Arg	synonymous_variant	Exon 9 of 12		XP_047282587.1
DLGAP3	XM_011541880.3	c.888C>A	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>A	p.Arg793Arg	synonymous_variant	Exon 9 of 12	5	NM_001080418.3	ENSP00000362444.1
DLGAP3	ENST00000235180.4	c.2379C>A	p.Arg793Arg	synonymous_variant	Exon 7 of 10	2		ENSP00000235180.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458568 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2 AN XY: 725828

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111960

Other (OTH) AF: 0.0000166 AC: 1 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Benign	0.73
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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;