20-36432411-C-A

Variant names:

• chr20-36432411-C-A
• rs145036695
• NM_001365621.2:c.694C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001365621.2(DLGAP4):​c.694C>A​(p.Arg232Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: DLGAP4 NM_001365621.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

Genes affected

DLGAP4 (HGNC:24476): (DLG associated protein 4) The product of this gene is a membrane-associated guanylate kinase found at the postsynaptic density in neuronal cells. It is a signaling molecule that can interact with potassium channels and receptors, as well as other signaling molecules. The protein encoded by this gene can interact with PSD-95 through its guanylate kinase domain and may be involved in clustering PSD-95 in the postsynaptic density region. The encoded protein is one of at least four similar proteins that have been found. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.828

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP4	NM_001365621.2	c.694C>A	p.Arg232Ser	missense_variant	Exon 3 of 13	ENST00000339266.10	NP_001352550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP4	ENST00000339266.10	c.694C>A	p.Arg232Ser	missense_variant	Exon 3 of 13	5	NM_001365621.2	ENSP00000341633.5
DLGAP4	ENST00000373913.7	c.694C>A	p.Arg232Ser	missense_variant	Exon 3 of 13	1		ENSP00000363023.3
DLGAP4	ENST00000373907.6	c.694C>A	p.Arg232Ser	missense_variant	Exon 2 of 12	5		ENSP00000363014.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	.;T;.;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	.;D;D;.
M_CAP	Uncertain	0.092	D
MetaRNN	Pathogenic	0.83	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;M;M;M
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.6	D;D;D;D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		1.0	D;.;D;.
Vest4		0.86
MutPred		0.55		Loss of MoRF binding (P = 0.0116);Loss of MoRF binding (P = 0.0116);Loss of MoRF binding (P = 0.0116);Loss of MoRF binding (P = 0.0116);
MVP		0.76
MPC		1.5
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.65
gMVP		0.65

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

Other links and lift over

dbSNP: rs145036695; hg19: chr20-35060814;