1-34868798-G-A

Position:

• chr1-34868798-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001080418.3(DLGAP3):​c.2292C>T​(p.Pro764Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,582,906 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0064 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00074 (8 hom.)
• Consequence: DLGAP3 NM_001080418.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.52

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 1-34868798-G-A is Benign according to our data. Variant chr1-34868798-G-A is described in ClinVar as [Benign]. Clinvar id is 786723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.52 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00637 (969/152220) while in subpopulation AFR AF= 0.0219 (911/41552). AF 95% confidence interval is 0.0207. There are 9 homozygotes in gnomad4. There are 481 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP3	NM_001080418.3	c.2292C>T	p.Pro764Pro	synonymous_variant	9/12	ENST00000373347.6	NP_001073887.1
DLGAP3	XM_011541879.3	c.2292C>T	p.Pro764Pro	synonymous_variant	10/13		XP_011540181.1
DLGAP3	XM_047426631.1	c.2292C>T	p.Pro764Pro	synonymous_variant	9/12		XP_047282587.1
DLGAP3	XM_011541880.3	c.801C>T	p.Pro267Pro	synonymous_variant	5/8		XP_011540182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP3	ENST00000373347.6	c.2292C>T	p.Pro764Pro	synonymous_variant	9/12	5	NM_001080418.3	ENSP00000362444.1
DLGAP3	ENST00000235180.4	c.2292C>T	p.Pro764Pro	synonymous_variant	7/10	2		ENSP00000235180.4

Frequencies

GnomAD3 genomes AF: 0.00636 AC: 968 AN: 152108 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0219

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00170 AC: 345 AN: 203030 Hom.: 0 AF XY: 0.00129 AC XY: 146 AN XY: 113304

Gnomad AFR exome AF: 0.0241

Gnomad AMR exome AF: 0.00112

Gnomad ASJ exome AF: 0.000791

Gnomad EAS exome AF: 0.0000608

Gnomad SAS exome AF: 0.000178

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000144

Gnomad OTH exome AF: 0.00133

GnomAD4 exome AF: 0.000735 AC: 1052 AN: 1430686 Hom.: 8 Cov.: 32 AF XY: 0.000682 AC XY: 484 AN XY: 709638

Gnomad4 AFR exome AF: 0.0227

Gnomad4 AMR exome AF: 0.00113

Gnomad4 ASJ exome AF: 0.00129

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.000106

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000926

Gnomad4 OTH exome AF: 0.00169

GnomAD4 genome AF: 0.00637 AC: 969 AN: 152220 Hom.: 9 Cov.: 32 AF XY: 0.00646 AC XY: 481 AN XY: 74430

Gnomad4 AFR AF: 0.0219

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.000860 Hom.: 1

Bravo AF: 0.00688

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.92
DANN	Benign	0.83

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: rs201441073; hg19: chr1-35334399;