Genetic Variant NM_004746.4:c.905C>T (chr18-3879164-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004746.4(DLGAP1):c.905C>T(p.Ala302Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000862 in 1,516,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00090 ( 0 hom. )

Consequence

DLGAP1
NM_004746.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.56

Publications

4 publications found

Variant links:

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 links:

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

DLGAP1-AS3 links:

LOC124904238 (HGNC:):

LOC124904238 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07311514).

BS2

High AC in GnomAd4 at 82 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DLGAP1	NM_004746.4	MANE Select	c.905C>T	p.Ala302Val	missense	Exon 4 of 13	NP_004737.2
DLGAP1	NM_001398525.1		c.905C>T	p.Ala302Val	missense	Exon 4 of 14	NP_001385454.1
DLGAP1	NM_001398526.1		c.905C>T	p.Ala302Val	missense	Exon 4 of 14	NP_001385455.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DLGAP1	ENST00000315677.8	TSL:5 MANE Select	c.905C>T	p.Ala302Val	missense	Exon 4 of 13	ENSP00000316377.3	O14490-1
DLGAP1	ENST00000498188.5	TSL:1	n.913C>T		non_coding_transcript_exon	Exon 1 of 5
DLGAP1-AS3	ENST00000577649.1	TSL:1	n.112+873G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000539

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000926

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000575

AC:

102

AN:

177326

AF XY:

0.000644

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.000189

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000587

Gnomad NFE exome

AF:

0.000954

Gnomad OTH exome

AF:

0.000493

GnomAD4 exome

AF:

0.000898

AC:

1225

AN:

1364366

Hom.:

Cov.:

AF XY:

0.000891

AC XY:

595

AN XY:

667968

show subpopulations

African (AFR)

AF:

0.0000661

AC:

AN:

30244

American (AMR)

AF:

0.000307

AC:

AN:

29320

Ashkenazi Jewish (ASJ)

AF:

0.0000502

AC:

AN:

19922

East Asian (EAS)

AF:

0.0000259

AC:

AN:

38566

South Asian (SAS)

AF:

0.0000426

AC:

AN:

70352

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

49722

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5310

European-Non Finnish (NFE)

AF:

0.00104

AC:

1110

AN:

1064840

Other (OTH)

AF:

0.000767

AC:

AN:

56090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

139

209

278

348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000538

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41578

American (AMR)

AF:

0.000196

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000753

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000926

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000788

Hom.:

Bravo

AF:

0.000567

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000470

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.49

Eigen

Uncertain

0.59

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.0091

MetaRNN

Benign

0.073

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.5

PhyloP100

9.6

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.1

REVEL

Benign

0.24

Sift

Benign

0.036

Sift4G

Uncertain

0.045

Polyphen

0.40

Vest4

0.53

MVP

0.35

MPC

0.60

ClinPred

0.042

GERP RS

5.5

Varity_R

0.31

gMVP

0.19

Mutation Taster

=67/33

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over