chr20-36431833-C-G

Variant names:

• chr20-36431833-C-G
• rs141542744
• NM_001365621.2:c.116C>G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001365621.2(DLGAP4):​c.116C>G​(p.Ala39Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: DLGAP4 NM_001365621.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.58

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08080828).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP4	NM_001365621.2	c.116C>G	p.Ala39Gly	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.116C>G	p.Ala39Gly	missense_variant	Exon 3 of 13	5	NM_001365621.2	ENSP00000341633.5
DLGAP4	ENST00000373913.7	c.116C>G	p.Ala39Gly	missense_variant	Exon 3 of 13	1		ENSP00000363023.3
DLGAP4	ENST00000373907.6	c.116C>G	p.Ala39Gly	missense_variant	Exon 2 of 12	5		ENSP00000363014.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 248196 Hom.: 0 AF XY: 0.00000744 AC XY: 1 AN XY: 134362

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461638 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727134

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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	Benign	0.089
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	19
DANN	Uncertain	0.97
DEOGEN2	Benign	0.018	.;T;.;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.079
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.71	.;T;T;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.081	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.73	N;N;N;N
REVEL	Benign	0.062
Sift	Benign	0.57	T;T;T;T
Sift4G	Benign	0.54	T;T;T;T
Polyphen		0.40	B;.;B;.
Vest4		0.32
MutPred		0.096		Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);
MVP		0.43
MPC		0.73
ClinPred		0.22	T
GERP RS		3.7
Varity_R		0.11
gMVP		0.53

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: rs141542744; hg19: chr20-35060236;