X-70445350-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_021120.4(DLG3):c.149G>C(p.Gly50Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000111 in 1,171,691 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000088 ( 0 hom., 0 hem., cov: 24)
Exomes 𝑓: 0.000011 ( 0 hom. 4 hem. )
Consequence
DLG3
NM_021120.4 missense
NM_021120.4 missense
Scores
2
14
Clinical Significance
Conservation
PhyloP100: 5.45
Genes affected
DLG3 (HGNC:2902): (discs large MAGUK scaffold protein 3) This gene encodes a member of the membrane-associated guanylate kinase protein family. The encoded protein may play a role in clustering of NMDA receptors at excitatory synapses. It may also negatively regulate cell proliferation through interaction with the C-terminal region of the adenomatosis polyposis coli tumor suppressor protein. Mutations in this gene have been associated with X-linked cognitive disability. Alternatively spliced transcript variants have been described. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.19466794).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DLG3 | NM_021120.4 | c.149G>C | p.Gly50Ala | missense_variant | 1/19 | ENST00000374360.8 | |
DLG3 | XM_006724625.3 | c.149G>C | p.Gly50Ala | missense_variant | 1/20 | ||
DLG3 | XM_011530883.2 | c.149G>C | p.Gly50Ala | missense_variant | 1/19 | ||
DLG3 | XM_006724626.3 | c.149G>C | p.Gly50Ala | missense_variant | 1/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DLG3 | ENST00000374360.8 | c.149G>C | p.Gly50Ala | missense_variant | 1/19 | 1 | NM_021120.4 | ||
DLG3 | ENST00000194900.8 | c.149G>C | p.Gly50Ala | missense_variant | 1/21 | 5 | P1 | ||
DLG3 | ENST00000463252.5 | n.215G>C | non_coding_transcript_exon_variant | 1/19 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000882 AC: 1AN: 113386Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 35526
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000906 AC: 1AN: 110349Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 36611
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GnomAD4 exome AF: 0.0000113 AC: 12AN: 1058305Hom.: 0 Cov.: 32 AF XY: 0.0000116 AC XY: 4AN XY: 344801
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 06, 2022 | The c.149G>C (p.G50A) alteration is located in exon 1 (coding exon 1) of the DLG3 gene. This alteration results from a G to C substitution at nucleotide position 149, causing the glycine (G) at amino acid position 50 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
0.0050
.;B
Vest4
MutPred
Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);
MVP
MPC
1.8
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at