rs141542744

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr20-36431833-C-T
• chr20-36431833-C-A
• chr20-36431833-C-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001365621.2(DLGAP4):​c.116C>T​(p.Ala39Val) variant causes a missense change. The variant allele was found at a frequency of 0.000604 in 1,613,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00061 (0 hom.)
• Consequence: DLGAP4 NM_001365621.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.58
• Publications: 7 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.032313377).
• BS2: High AC in GnomAd4 at 80 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP4	NM_001365621.2	MANE Select	c.116C>T	p.Ala39Val	missense	Exon 3 of 13	NP_001352550.1	Q9Y2H0-2
	DLGAP4	NM_014902.6		c.116C>T	p.Ala39Val	missense	Exon 3 of 13	NP_055717.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP4	ENST00000339266.10	TSL:5 MANE Select	c.116C>T	p.Ala39Val	missense	Exon 3 of 13	ENSP00000341633.5	Q9Y2H0-2
	DLGAP4	ENST00000373913.7	TSL:1	c.116C>T	p.Ala39Val	missense	Exon 3 of 13	ENSP00000363023.3	Q9Y2H0-1
	DLGAP4	ENST00000373907.6	TSL:5	c.116C>T	p.Ala39Val	missense	Exon 2 of 12	ENSP00000363014.2	Q9Y2H0-2

Frequencies

GnomAD3 genomes AF: 0.000526 AC: 80 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000941

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000379 AC: 94 AN: 248196 AF XY: 0.000357

Gnomad AFR exome AF: 0.0000624

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.000904

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000639

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.000612 AC: 895 AN: 1461638 Hom.: 0 Cov.: 31 AF XY: 0.000620 AC XY: 451 AN XY: 727134

African (AFR) AF: 0.0000597 AC: 2 AN: 33476

American (AMR) AF: 0.0000447 AC: 2 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00157 AC: 41 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.000113 AC: 6 AN: 53306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000734 AC: 816 AN: 1111936

Other (OTH) AF: 0.000447 AC: 27 AN: 60382

GnomAD4 genome AF: 0.000526 AC: 80 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.000390 AC XY: 29 AN XY: 74350

African (AFR) AF: 0.000169 AC: 7 AN: 41456

American (AMR) AF: 0.000196 AC: 3 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000941 AC: 64 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000641 Hom.: 0

Bravo AF: 0.000412

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00151 AC: 13

ExAC AF: 0.000338 AC: 41

EpiCase AF: 0.000654

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.062
Eigen_PC	Benign	0.054
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		3.6
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.033
Sift	Benign	0.14	T
Sift4G	Benign	0.17	T
Polyphen		0.40	B
Vest4		0.24
MVP		0.42
MPC		0.72
ClinPred		0.021	T
GERP RS		3.7
Varity_R		0.091
gMVP		0.60
Mutation Taster		=93/7	polymorphism

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: rs141542744; hg19: chr20-35060236; COSMIC: COSV59420054;