NM_004746.4:c.1551G>A

Variant names:

• chr18-3729175-C-T
• rs3745051
• NM_004746.4:c.1551G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_004746.4(DLGAP1):​c.1551G>A​(p.Pro517Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,612,722 control chromosomes in the GnomAD database, including 18,210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.18 (3235 hom., cov: 32)
  • Exomes 𝑓: 0.13 (14975 hom.)
• Consequence: DLGAP1 NM_004746.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.480
• Publications: 15 publications found

Genes affected

DLGAP1 (HGNC:2905): (DLG associated protein 1) Predicted to enable molecular adaptor activity. Predicted to be a structural constituent of postsynaptic density. Predicted to be involved in several processes, including aggresome assembly; regulation of postsynaptic neurotransmitter receptor activity; and regulation of proteasomal protein catabolic process. Predicted to be located in plasma membrane. Predicted to be part of postsynaptic density. Predicted to be active in glutamatergic synapse and postsynaptic density, intracellular component. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 18-3729175-C-T is Benign according to our data. Variant chr18-3729175-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060604.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.48 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004746.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP1	NM_004746.4	MANE Select	c.1551G>A	p.Pro517Pro	synonymous	Exon 7 of 13	NP_004737.2
	DLGAP1	NM_001398525.1		c.1551G>A	p.Pro517Pro	synonymous	Exon 7 of 14	NP_001385454.1
	DLGAP1	NM_001398526.1		c.1551G>A	p.Pro517Pro	synonymous	Exon 7 of 14	NP_001385455.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP1	ENST00000315677.8	TSL:5 MANE Select	c.1551G>A	p.Pro517Pro	synonymous	Exon 7 of 13	ENSP00000316377.3	O14490-1
	DLGAP1	ENST00000400147.6	TSL:1	c.645G>A	p.Pro215Pro	synonymous	Exon 4 of 10	ENSP00000383011.2	O14490-2
	DLGAP1	ENST00000400145.6	TSL:1	c.645G>A	p.Pro215Pro	synonymous	Exon 4 of 9	ENSP00000383010.2	O14490-3

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27791 AN: 151956 Hom.: 3232 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.170

GnomAD2 exomes AF: 0.163 AC: 40490 AN: 247898 AF XY: 0.161

Gnomad AFR exome AF: 0.313

Gnomad AMR exome AF: 0.133

Gnomad ASJ exome AF: 0.170

Gnomad EAS exome AF: 0.335

Gnomad FIN exome AF: 0.163

Gnomad NFE exome AF: 0.109

Gnomad OTH exome AF: 0.150

GnomAD4 exome AF: 0.131 AC: 190888 AN: 1460646 Hom.: 14975 Cov.: 33 AF XY: 0.133 AC XY: 96739 AN XY: 726602

African (AFR) AF: 0.304 AC: 10190 AN: 33466

American (AMR) AF: 0.137 AC: 6103 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 4419 AN: 26090

East Asian (EAS) AF: 0.337 AC: 13365 AN: 39672

South Asian (SAS) AF: 0.219 AC: 18818 AN: 86098

European-Finnish (FIN) AF: 0.150 AC: 7935 AN: 52998

Middle Eastern (MID) AF: 0.227 AC: 1303 AN: 5730

European-Non Finnish (NFE) AF: 0.107 AC: 119265 AN: 1111606

Other (OTH) AF: 0.157 AC: 9490 AN: 60352

GnomAD4 genome AF: 0.183 AC: 27812 AN: 152076 Hom.: 3235 Cov.: 32 AF XY: 0.185 AC XY: 13771 AN XY: 74346

African (AFR) AF: 0.303 AC: 12549 AN: 41468

American (AMR) AF: 0.141 AC: 2151 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 567 AN: 3472

East Asian (EAS) AF: 0.346 AC: 1782 AN: 5146

South Asian (SAS) AF: 0.224 AC: 1079 AN: 4822

European-Finnish (FIN) AF: 0.165 AC: 1747 AN: 10582

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7446 AN: 67980

Other (OTH) AF: 0.166 AC: 350 AN: 2108

Alfa AF: 0.128 Hom.: 2376

Bravo AF: 0.186

Asia WGS AF: 0.249 AC: 865 AN: 3478

EpiCase AF: 0.119

EpiControl AF: 0.112

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DLGAP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	6.9
DANN	Benign	0.68
PhyloP100		-0.48
Mutation Taster		=93/7	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3745051; hg19: chr18-3729175; COSMIC: COSV59792373;