chr1-34867325-G-C

Variant names:

• chr1-34867325-G-C
• rs1001616
• NM_001080418.3:c.2578-134C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080418.3(DLGAP3):​c.2578-134C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 1,343,748 control chromosomes in the GnomAD database, including 77,074 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (7863 hom., cov: 32)
  • Exomes 𝑓: 0.32 (69211 hom.)
• Consequence: DLGAP3 NM_001080418.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080418.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP3	NM_001080418.3	MANE Select	c.2578-134C>G		intron	N/A	NP_001073887.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP3	ENST00000373347.6	TSL:5 MANE Select	c.2578-134C>G		intron	N/A	ENSP00000362444.1
	DLGAP3	ENST00000235180.4	TSL:2	c.2578-134C>G		intron	N/A	ENSP00000235180.4

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42732 AN: 151864 Hom.: 7847 Cov.: 32

Gnomad AFR AF: 0.0988

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.290

GnomAD4 exome AF: 0.318 AC: 378404 AN: 1191766 Hom.: 69211 AF XY: 0.323 AC XY: 194450 AN XY: 602940

African (AFR) AF: 0.0877 AC: 2501 AN: 28512

American (AMR) AF: 0.502 AC: 20142 AN: 40128

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 7405 AN: 24140

East Asian (EAS) AF: 0.847 AC: 31857 AN: 37632

South Asian (SAS) AF: 0.454 AC: 36023 AN: 79302

European-Finnish (FIN) AF: 0.374 AC: 17344 AN: 46372

Middle Eastern (MID) AF: 0.339 AC: 1716 AN: 5062

European-Non Finnish (NFE) AF: 0.278 AC: 244520 AN: 878868

Other (OTH) AF: 0.326 AC: 16896 AN: 51750

GnomAD4 genome AF: 0.281 AC: 42770 AN: 151982 Hom.: 7863 Cov.: 32 AF XY: 0.297 AC XY: 22032 AN XY: 74286

African (AFR) AF: 0.0990 AC: 4107 AN: 41488

American (AMR) AF: 0.429 AC: 6549 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1095 AN: 3466

East Asian (EAS) AF: 0.831 AC: 4275 AN: 5142

South Asian (SAS) AF: 0.467 AC: 2248 AN: 4816

European-Finnish (FIN) AF: 0.375 AC: 3957 AN: 10564

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19662 AN: 67920

Other (OTH) AF: 0.298 AC: 629 AN: 2110

Alfa AF: 0.172 Hom.: 379

Bravo AF: 0.274

Asia WGS AF: 0.607 AC: 2112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.2
DANN	Benign	0.81
PhyloP100		-1.3
Mutation Taster		=100/0	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: rs1001616; hg19: chr1-35332926; COSMIC: COSV52391114;