1-34904466-G-A

Variant names:

• chr1-34904466-G-A
• rs141540099
• NM_001080418.3:c.918C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001080418.3(DLGAP3):​c.918C>T​(p.Gly306Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00284 in 1,614,114 control chromosomes in the GnomAD database, including 193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (26 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (167 hom.)
• Consequence: DLGAP3 NM_001080418.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.960
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 1-34904466-G-A is Benign according to our data. Variant chr1-34904466-G-A is described in ClinVar as [Benign]. Clinvar id is 778796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.96 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP3	NM_001080418.3	c.918C>T	p.Gly306Gly	synonymous_variant	Exon 3 of 12	ENST00000373347.6	NP_001073887.1
DLGAP3	XM_011541879.3	c.918C>T	p.Gly306Gly	synonymous_variant	Exon 4 of 13		XP_011540181.1
DLGAP3	XM_047426631.1	c.918C>T	p.Gly306Gly	synonymous_variant	Exon 3 of 12		XP_047282587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP3	ENST00000373347.6	c.918C>T	p.Gly306Gly	synonymous_variant	Exon 3 of 12	5	NM_001080418.3	ENSP00000362444.1
DLGAP3	ENST00000235180.4	c.918C>T	p.Gly306Gly	synonymous_variant	Exon 1 of 10	2		ENSP00000235180.4

Frequencies

GnomAD3 genomes AF: 0.00451 AC: 686 AN: 152180 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0352

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00502

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.00861

GnomAD2 exomes AF: 0.0106 AC: 2661 AN: 251106 AF XY: 0.00777

Gnomad AFR exome AF: 0.00130

Gnomad AMR exome AF: 0.0692

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00539

Gnomad FIN exome AF: 0.000788

Gnomad NFE exome AF: 0.000493

Gnomad OTH exome AF: 0.00945

GnomAD4 exome AF: 0.00266 AC: 3889 AN: 1461816 Hom.: 167 Cov.: 33 AF XY: 0.00229 AC XY: 1668 AN XY: 727218

African (AFR) AF: 0.00102 AC: 34 AN: 33480

American (AMR) AF: 0.0662 AC: 2959 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00768 AC: 305 AN: 39700

South Asian (SAS) AF: 0.000510 AC: 44 AN: 86258

European-Finnish (FIN) AF: 0.000881 AC: 47 AN: 53350

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

European-Non Finnish (NFE) AF: 0.000298 AC: 331 AN: 1112006

Other (OTH) AF: 0.00280 AC: 169 AN: 60394

GnomAD4 genome AF: 0.00454 AC: 692 AN: 152298 Hom.: 26 Cov.: 32 AF XY: 0.00471 AC XY: 351 AN XY: 74476

African (AFR) AF: 0.00125 AC: 52 AN: 41564

American (AMR) AF: 0.0355 AC: 544 AN: 15310

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

East Asian (EAS) AF: 0.00503 AC: 26 AN: 5170

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4834

European-Finnish (FIN) AF: 0.000942 AC: 10 AN: 10618

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

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 68014

Other (OTH) AF: 0.00852 AC: 18 AN: 2112

Alfa AF: 0.000977 Hom.: 1

Bravo AF: 0.00708

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	2.5
DANN	Benign	0.70
PhyloP100		-0.96
Mutation Taster		=98/2	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: rs141540099; hg19: chr1-35370067; COSMIC: COSV104580661; COSMIC: COSV104580661;