chr20-36420192-T-C

Variant names:

• chr20-36420192-T-C
• rs906467
• NM_001365621.2:c.-72-11454T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365621.2(DLGAP4):​c.-72-11454T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.081 in 152,238 control chromosomes in the GnomAD database, including 682 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.081 (682 hom., cov: 33)
• Consequence: DLGAP4 NM_001365621.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.915
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365621.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP4	NM_001365621.2	MANE Select	c.-72-11454T>C		intron	N/A	NP_001352550.1
	DLGAP4	NM_014902.6		c.-72-11454T>C		intron	N/A	NP_055717.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP4	ENST00000339266.10	TSL:5 MANE Select	c.-72-11454T>C		intron	N/A	ENSP00000341633.5
	DLGAP4	ENST00000373913.7	TSL:1	c.-72-11454T>C		intron	N/A	ENSP00000363023.3
	DLGAP4	ENST00000373907.6	TSL:5	c.-72-11454T>C		intron	N/A	ENSP00000363014.2

Frequencies

GnomAD3 genomes AF: 0.0810 AC: 12315 AN: 152120 Hom.: 679 Cov.: 33

Gnomad AFR AF: 0.0713

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.0665

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.0387

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0727

Gnomad OTH AF: 0.0837

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0810 AC: 12331 AN: 152238 Hom.: 682 Cov.: 33 AF XY: 0.0823 AC XY: 6124 AN XY: 74452

African (AFR) AF: 0.0713 AC: 2963 AN: 41556

American (AMR) AF: 0.0667 AC: 1020 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 375 AN: 3470

East Asian (EAS) AF: 0.233 AC: 1206 AN: 5166

South Asian (SAS) AF: 0.231 AC: 1113 AN: 4820

European-Finnish (FIN) AF: 0.0387 AC: 411 AN: 10616

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0727 AC: 4942 AN: 67998

Other (OTH) AF: 0.0866 AC: 183 AN: 2114

Alfa AF: 0.0731 Hom.: 202

Bravo AF: 0.0809

Asia WGS AF: 0.231 AC: 803 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.44
DANN	Benign	0.43
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs906467; hg19: chr20-35048595;