Genetic Variant PASD1:p.Pro162Ser (chrX-151623002-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_173493.3(PASD1):c.484C>T(p.Pro162Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000191 in 1,207,203 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P162R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.000017 ( 0 hom. 5 hem. )

Consequence

PASD1
NM_173493.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.357

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PASD1	NM_173493.3 link	c.484C>T	p.Pro162Ser	missense_variant	Exon 7 of 16	ENST00000370357.5	NP_775764.2
PASD1	XM_011531102.3 link	c.484C>T	p.Pro162Ser	missense_variant	Exon 7 of 16		XP_011529404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PASD1	ENST00000370357.5 link	c.484C>T	p.Pro162Ser	missense_variant	Exon 7 of 16	1	NM_173493.3	ENSP00000359382.4		Q8IV76-1
PASD1	ENST00000464219.1 link	n.622C>T		non_coding_transcript_exon_variant	Exon 7 of 15	2

Frequencies

GnomAD3 genomes

AF:

0.0000358

AC:

AN:

111618

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000564

Gnomad OTH

AF:

0.000669

GnomAD2 exomes

AF:

0.0000329

AC:

AN:

182260

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000491

Gnomad OTH exome

AF:

0.000447

GnomAD4 exome

AF:

0.0000173

AC:

AN:

1095585

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

361183

show subpopulations

African (AFR)

AF:

0.0000380

AC:

AN:

26343

American (AMR)

AF:

0.00

AC:

AN:

35163

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19351

East Asian (EAS)

AF:

0.00

AC:

AN:

30175

South Asian (SAS)

AF:

0.00

AC:

AN:

53948

European-Finnish (FIN)

AF:

0.0000247

AC:

AN:

40521

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4131

European-Non Finnish (NFE)

AF:

0.0000202

AC:

AN:

839946

Other (OTH)

AF:

0.00

AC:

AN:

46007

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000358

AC:

AN:

111618

Hom.:

Cov.:

AF XY:

0.0000887

AC XY:

AN XY:

33810

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30660

American (AMR)

AF:

0.00

AC:

AN:

10484

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3544

South Asian (SAS)

AF:

0.00

AC:

AN:

2632

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6071

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000564

AC:

AN:

53156

Other (OTH)

AF:

0.000669

AC:

AN:

1495

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000324

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 29, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.484C>T (p.P162S) alteration is located in exon 7 (coding exon 6) of the PASD1 gene. This alteration results from a C to T substitution at nucleotide position 484, causing the proline (P) at amino acid position 162 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.3

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0023

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.37

M_CAP

Benign

0.012

MetaRNN

Benign

0.081

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.65

PhyloP100

-0.36

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.040

REVEL

Benign

0.032

Sift

Benign

0.039

Sift4G

Uncertain

0.045

Polyphen

0.61

Vest4

0.044

MutPred

0.47

Loss of loop (P = 0.0986);

MVP

0.082

MPC

0.039

ClinPred

0.038

GERP RS

2.0

Varity_R

0.027

gMVP

0.18

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: 6

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

Publications

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X-151623002-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over