dbSNP rs5924658: PASD1:p.Gln213Glu (chrX-151648622-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_173493.3(PASD1):c.637C>G(p.Gln213Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,207,244 control chromosomes in the GnomAD database, including 28,515 homozygotes. There are 100,240 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 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: 𝑓 0.20 ( 2041 hom., 6303 hem., cov: 22)

Exomes 𝑓: 0.26 ( 26474 hom. 93937 hem. )

Consequence

PASD1
NM_173493.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.754

Publications

15 publications found

Variant links:

Genes affected

PASD1 (HGNC:20686): (PAS domain containing repressor 1) This gene encodes a protein that is thought to function as a transcription factor. The protein is a cancer-associated antigen that can stimulate autologous T-cell responses, and it is therefore considered to be a potential immunotherapeutic target for the treatment of various hematopoietic malignancies, including diffuse large B-cell lymphoma. [provided by RefSeq, May 2010]

PASD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0056649745).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PASD1	NM_173493.3 link	c.637C>G	p.Gln213Glu	missense_variant	Exon 9 of 16	ENST00000370357.5	NP_775764.2
PASD1	XM_011531102.3 link	c.637C>G	p.Gln213Glu	missense_variant	Exon 9 of 16		XP_011529404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PASD1	ENST00000370357.5 link	c.637C>G	p.Gln213Glu	missense_variant	Exon 9 of 16	1	NM_173493.3	ENSP00000359382.4		Q8IV76-1
PASD1	ENST00000464219.1 link	n.775C>G		non_coding_transcript_exon_variant	Exon 9 of 15	2

Frequencies

GnomAD3 genomes

AF:

0.197

AC:

21810

AN:

110911

Hom.:

2042

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0409

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.0272

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.285

Gnomad MID

AF:

0.289

Gnomad NFE

AF:

0.276

Gnomad OTH

AF:

0.227

GnomAD2 exomes

AF:

0.230

AC:

41663

AN:

180824

AF XY:

0.236

show subpopulations

Gnomad AFR exome

AF:

0.0354

Gnomad AMR exome

AF:

0.248

Gnomad ASJ exome

AF:

0.308

Gnomad EAS exome

AF:

0.0175

Gnomad FIN exome

AF:

0.311

Gnomad NFE exome

AF:

0.280

Gnomad OTH exome

AF:

0.251

GnomAD4 exome

AF:

0.261

AC:

286135

AN:

1096278

Hom.:

26474

Cov.:

AF XY:

0.260

AC XY:

93937

AN XY:

361972

show subpopulations

African (AFR)

AF:

0.0342

AC:

903

AN:

26378

American (AMR)

AF:

0.243

AC:

8558

AN:

35150

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

5960

AN:

19349

East Asian (EAS)

AF:

0.0352

AC:

1063

AN:

30195

South Asian (SAS)

AF:

0.186

AC:

9996

AN:

53878

European-Finnish (FIN)

AF:

0.314

AC:

12696

AN:

40490

Middle Eastern (MID)

AF:

0.260

AC:

1071

AN:

4127

European-Non Finnish (NFE)

AF:

0.279

AC:

234662

AN:

840690

Other (OTH)

AF:

0.244

AC:

11226

AN:

46021

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

6883

13766

20650

27533

34416

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8196

16392

24588

32784

40980

<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:

0.196

AC:

21798

AN:

110966

Hom.:

2041

Cov.:

AF XY:

0.190

AC XY:

6303

AN XY:

33210

show subpopulations

African (AFR)

AF:

0.0408

AC:

1252

AN:

30652

American (AMR)

AF:

0.230

AC:

2396

AN:

10413

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

811

AN:

2631

East Asian (EAS)

AF:

0.0276

AC:

AN:

3555

South Asian (SAS)

AF:

0.185

AC:

483

AN:

2615

European-Finnish (FIN)

AF:

0.285

AC:

1656

AN:

5805

Middle Eastern (MID)

AF:

0.280

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.276

AC:

14593

AN:

52889

Other (OTH)

AF:

0.224

AC:

339

AN:

1511

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

590

1180

1769

2359

2949

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

224

448

672

896

1120

<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:

0.243

Hom.:

2198

Bravo

AF:

0.187

TwinsUK

AF:

0.280

AC:

1040

ALSPAC

AF:

0.286

AC:

827

ESP6500AA

AF:

0.0415

AC:

159

ESP6500EA

AF:

0.277

AC:

1861

ExAC

AF:

0.227

AC:

27534

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.2

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0014

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0057

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

-0.75

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.35

REVEL

Benign

0.070

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.027

Polyphen

0.74

Vest4

0.049

MPC

0.12

ClinPred

0.0089

GERP RS

1.1

Varity_R

0.087

gMVP

0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over