1-34900163-G-A

Variant names:

• chr1-34900163-G-A
• rs150566254
• NM_001080418.3:c.1218C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001080418.3(DLGAP3):​c.1218C>T​(p.Ser406Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000774 in 1,613,976 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0010 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00075 (8 hom.)
• Consequence: DLGAP3 NM_001080418.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0210
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 1-34900163-G-A is Benign according to our data. Variant chr1-34900163-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 724007.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.021 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP3	NM_001080418.3	c.1218C>T	p.Ser406Ser	synonymous_variant	Exon 4 of 12	ENST00000373347.6	NP_001073887.1
DLGAP3	XM_011541879.3	c.1218C>T	p.Ser406Ser	synonymous_variant	Exon 5 of 13		XP_011540181.1
DLGAP3	XM_047426631.1	c.1218C>T	p.Ser406Ser	synonymous_variant	Exon 4 of 12		XP_047282587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP3	ENST00000373347.6	c.1218C>T	p.Ser406Ser	synonymous_variant	Exon 4 of 12	5	NM_001080418.3	ENSP00000362444.1
DLGAP3	ENST00000235180.4	c.1218C>T	p.Ser406Ser	synonymous_variant	Exon 2 of 10	2		ENSP00000235180.4

Frequencies

GnomAD3 genomes AF: 0.00101 AC: 154 AN: 152172 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.0354

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00133 AC: 334 AN: 251350 AF XY: 0.00133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.0263

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000440

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000749 AC: 1095 AN: 1461686 Hom.: 8 Cov.: 32 AF XY: 0.000773 AC XY: 562 AN XY: 727152

African (AFR) AF: 0.0000597 AC: 2 AN: 33478

American (AMR) AF: 0.000291 AC: 13 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0272 AC: 710 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53240

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

European-Non Finnish (NFE) AF: 0.000218 AC: 242 AN: 1111988

Other (OTH) AF: 0.00205 AC: 124 AN: 60394

GnomAD4 genome AF: 0.00101 AC: 154 AN: 152290 Hom.: 1 Cov.: 32 AF XY: 0.000953 AC XY: 71 AN XY: 74466

African (AFR) AF: 0.0000722 AC: 3 AN: 41572

American (AMR) AF: 0.000327 AC: 5 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0354 AC: 123 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68022

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00262 Hom.: 0

Bravo AF: 0.00102

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.00113

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DLGAP3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	3.8
DANN	Benign	0.85
PhyloP100		-0.021
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: rs150566254; hg19: chr1-35365764; COSMIC: COSV52393755;