rs76205593

Variant names:

• chr18-3879739-C-G
• rs76205593
• NM_004746.4:c.330G>C

Your query was ambiguous. Multiple possible variants found:

• chr18-3879739-C-G
• chr18-3879739-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004746.4(DLGAP1):​c.330G>C​(p.Gln110His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,472 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DLGAP1 NM_004746.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.52
• Publications: 5 publications found

Genes affected

DLGAP1 (HGNC:2905): (DLG associated protein 1) Predicted to enable molecular adaptor activity. Predicted to be a structural constituent of postsynaptic density. Predicted to be involved in several processes, including aggresome assembly; regulation of postsynaptic neurotransmitter receptor activity; and regulation of proteasomal protein catabolic process. Predicted to be located in plasma membrane. Predicted to be part of postsynaptic density. Predicted to be active in glutamatergic synapse and postsynaptic density, intracellular component. [provided by Alliance of Genome Resources, Apr 2022]

DLGAP1-AS3 (HGNC:27317): (DLGAP1 antisense RNA 3)

LOC124904238 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004746.4. 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
	DLGAP1	NM_004746.4	MANE Select	c.330G>C	p.Gln110His	missense	Exon 4 of 13	NP_004737.2
	DLGAP1	NM_001398525.1		c.330G>C	p.Gln110His	missense	Exon 4 of 14	NP_001385454.1
	DLGAP1	NM_001398526.1		c.330G>C	p.Gln110His	missense	Exon 4 of 14	NP_001385455.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP1	ENST00000315677.8	TSL:5 MANE Select	c.330G>C	p.Gln110His	missense	Exon 4 of 13	ENSP00000316377.3
	DLGAP1	ENST00000498188.5	TSL:1	n.338G>C		non_coding_transcript_exon	Exon 1 of 5
	DLGAP1-AS3	ENST00000577649.1	TSL:1	n.112+1448C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455472 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724398

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111794

Other (OTH) AF: 0.00 AC: 0 AN: 60268

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000829 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.5
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.29
Sift	Benign	0.051	T
Sift4G	Benign	0.092	T
Polyphen		0.85	P
Vest4		0.87
MutPred		0.41		Gain of disorder (P = 0.1779)
MVP		0.73
MPC		1.1
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.38
gMVP		0.74
Mutation Taster		=64/36	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: rs76205593; hg19: chr18-3879739;