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GeneBe

1-34868798-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001080418.3(DLGAP3):c.2292C>T(p.Pro764=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,582,906 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0064 ( 9 hom., cov: 32)
Exomes 𝑓: 0.00074 ( 8 hom. )

Consequence

DLGAP3
NM_001080418.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.52
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-34868798-G-A is Benign according to our data. Variant chr1-34868798-G-A is described in ClinVar as [Benign]. Clinvar id is 786723.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.52 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00637 (969/152220) while in subpopulation AFR AF= 0.0219 (911/41552). AF 95% confidence interval is 0.0207. There are 9 homozygotes in gnomad4. There are 481 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 9 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DLGAP3NM_001080418.3 linkuse as main transcriptc.2292C>T p.Pro764= synonymous_variant 9/12 ENST00000373347.6
DLGAP3XM_011541879.3 linkuse as main transcriptc.2292C>T p.Pro764= synonymous_variant 10/13
DLGAP3XM_047426631.1 linkuse as main transcriptc.2292C>T p.Pro764= synonymous_variant 9/12
DLGAP3XM_011541880.3 linkuse as main transcriptc.801C>T p.Pro267= synonymous_variant 5/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DLGAP3ENST00000373347.6 linkuse as main transcriptc.2292C>T p.Pro764= synonymous_variant 9/125 NM_001080418.3 P1
DLGAP3ENST00000235180.4 linkuse as main transcriptc.2292C>T p.Pro764= synonymous_variant 7/102 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00636
AC:
968
AN:
152108
Hom.:
9
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0219
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00164
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00318
Gnomad NFE
AF:
0.000265
Gnomad OTH
AF:
0.00430
GnomAD3 exomes
AF:
0.00170
AC:
345
AN:
203030
Hom.:
0
AF XY:
0.00129
AC XY:
146
AN XY:
113304
show subpopulations
Gnomad AFR exome
AF:
0.0241
Gnomad AMR exome
AF:
0.00112
Gnomad ASJ exome
AF:
0.000791
Gnomad EAS exome
AF:
0.0000608
Gnomad SAS exome
AF:
0.000178
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000144
Gnomad OTH exome
AF:
0.00133
GnomAD4 exome
AF:
0.000735
AC:
1052
AN:
1430686
Hom.:
8
Cov.:
32
AF XY:
0.000682
AC XY:
484
AN XY:
709638
show subpopulations
Gnomad4 AFR exome
AF:
0.0227
Gnomad4 AMR exome
AF:
0.00113
Gnomad4 ASJ exome
AF:
0.00129
Gnomad4 EAS exome
AF:
0.0000256
Gnomad4 SAS exome
AF:
0.000106
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000926
Gnomad4 OTH exome
AF:
0.00169
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00637
AC:
969
AN:
152220
Hom.:
9
Cov.:
32
AF XY:
0.00646
AC XY:
481
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.0219
Gnomad4 AMR
AF:
0.00163
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000265
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.000860
Hom.:
1
Bravo
AF:
0.00688
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
Cadd
Benign
0.92
Dann
Benign
0.83

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201441073; hg19: chr1-35334399; API