17-7196492-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001321075.3(DLG4):​c.1167C>G​(p.Ile389Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

DLG4
NM_001321075.3 missense

Scores

6
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.74
Variant links:
Genes affected
DLG4 (HGNC:2903): (discs large MAGUK scaffold protein 4) This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. It heteromultimerizes with another MAGUK protein, DLG2, and is recruited into NMDA receptor and potassium channel clusters. These two MAGUK proteins may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DLG4NM_001321075.3 linkc.1167C>G p.Ile389Met missense_variant Exon 10 of 20 ENST00000399506.9 NP_001308004.1 P78352-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DLG4ENST00000399506.9 linkc.1167C>G p.Ile389Met missense_variant Exon 10 of 20 2 NM_001321075.3 ENSP00000382425.2 P78352-1
DLG4ENST00000648172.8 linkc.1296C>G p.Ile432Met missense_variant Exon 12 of 22 ENSP00000497806.3 P78352-2
DLG4ENST00000648896.1 linkc.1266C>G p.Ile422Met missense_variant Exon 10 of 20 ENSP00000497546.1 A0A3B3ISQ5
DLG4ENST00000649520.1 linkc.987C>G p.Ile329Met missense_variant Exon 9 of 19 ENSP00000497647.1 B7Z647
DLG4ENST00000648263.1 linkc.987C>G p.Ile329Met missense_variant Exon 8 of 14 ENSP00000498035.1 A0A3B3IU19
DLG4ENST00000491753.2 linkn.1296C>G non_coding_transcript_exon_variant Exon 12 of 21 2 ENSP00000467897.2 B7Z3U2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
39
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.088
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Benign
0.41
.;.;T;T;T;.;T;.;.;.
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.61
FATHMM_MKL
Benign
0.17
N
LIST_S2
Uncertain
0.88
D;D;D;.;D;D;D;D;D;D
M_CAP
Benign
0.018
T
MetaRNN
Uncertain
0.48
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.3
.;.;L;.;.;.;.;.;.;.
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-1.6
.;N;N;.;.;.;.;.;.;.
REVEL
Benign
0.18
Sift
Uncertain
0.012
.;D;D;.;.;.;.;.;.;.
Sift4G
Uncertain
0.046
.;D;D;.;.;.;.;.;.;.
Polyphen
0.90
P;.;P;.;P;.;.;.;.;.
Vest4
0.42, 0.42
MutPred
0.46
.;.;Loss of methylation at K393 (P = 0.1106);.;.;.;.;.;.;.;
MVP
0.80
MPC
2.3
ClinPred
0.69
D
GERP RS
-2.8
Varity_R
0.14
gMVP
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs17203281; hg19: chr17-7099811; API