chr1-34868849-G-A

Variant names:

• chr1-34868849-G-A
• rs11587343
• NM_001080418.3:c.2241C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001080418.3(DLGAP3):​c.2241C>T​(p.Tyr747Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,586,072 control chromosomes in the GnomAD database, including 10 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 0.0019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (10 hom.)
• Consequence: DLGAP3 NM_001080418.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 2 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=-1.1 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 10 gene

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.2241C>T	p.Tyr747Tyr	synonymous	Exon 9 of 12	NP_001073887.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP3	ENST00000373347.6	TSL:5 MANE Select	c.2241C>T	p.Tyr747Tyr	synonymous	Exon 9 of 12	ENSP00000362444.1
	DLGAP3	ENST00000235180.4	TSL:2	c.2241C>T	p.Tyr747Tyr	synonymous	Exon 7 of 10	ENSP00000235180.4

Frequencies

GnomAD3 genomes AF: 0.00188 AC: 286 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00368

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00183 AC: 387 AN: 211766 AF XY: 0.00179

Gnomad AFR exome AF: 0.000806

Gnomad AMR exome AF: 0.000122

Gnomad ASJ exome AF: 0.000112

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000877

Gnomad NFE exome AF: 0.00369

Gnomad OTH exome AF: 0.00225

GnomAD4 exome AF: 0.00305 AC: 4372 AN: 1433780 Hom.: 10 Cov.: 32 AF XY: 0.00296 AC XY: 2108 AN XY: 711682

African (AFR) AF: 0.000514 AC: 17 AN: 33106

American (AMR) AF: 0.000184 AC: 8 AN: 43432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25542

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39142

South Asian (SAS) AF: 0.000153 AC: 13 AN: 84932

European-Finnish (FIN) AF: 0.000356 AC: 14 AN: 39374

Middle Eastern (MID) AF: 0.000351 AC: 2 AN: 5690

European-Non Finnish (NFE) AF: 0.00381 AC: 4208 AN: 1103162

Other (OTH) AF: 0.00184 AC: 109 AN: 59400

GnomAD4 genome AF: 0.00188 AC: 287 AN: 152292 Hom.: 0 Cov.: 32 AF XY: 0.00181 AC XY: 135 AN XY: 74464

African (AFR) AF: 0.000673 AC: 28 AN: 41574

American (AMR) AF: 0.000196 AC: 3 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00368 AC: 250 AN: 68008

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00204 Hom.: 1

Bravo AF: 0.00169

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.44
DANN	Benign	0.71
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism

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: rs11587343; hg19: chr1-35334450; COSMIC: COSV99333228;