Genetic Variant PASD1:p.Cys174Phe (chrX-151623039-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_173493.3(PASD1):c.521G>T(p.Cys174Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., 0 hem., cov: 23)

Failed GnomAD Quality Control

Consequence

PASD1
NM_173493.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.991

Publications

0 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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29933196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PASD1	NM_173493.3 link	c.521G>T	p.Cys174Phe	missense_variant	Exon 7 of 16	ENST00000370357.5	NP_775764.2
PASD1	XM_011531102.3 link	c.521G>T	p.Cys174Phe	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.521G>T	p.Cys174Phe	missense_variant	Exon 7 of 16	1	NM_173493.3	ENSP00000359382.4		Q8IV76-1
PASD1	ENST00000464219.1 link	n.659G>T		non_coding_transcript_exon_variant	Exon 7 of 15	2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

111604

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

111604

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33776

African (AFR)

AF:

0.00

AC:

AN:

30646

American (AMR)

AF:

0.00

AC:

AN:

10471

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2643

East Asian (EAS)

AF:

0.00

AC:

AN:

3548

South Asian (SAS)

AF:

0.00

AC:

AN:

2640

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6082

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53150

Other (OTH)

AF:

0.00

AC:

AN:

1500

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000491

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 11, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.521G>T (p.C174F) alteration is located in exon 7 (coding exon 6) of the PASD1 gene. This alteration results from a G to T substitution at nucleotide position 521, causing the cysteine (C) at amino acid position 174 to be replaced by a phenylalanine (F). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.014

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.37

M_CAP

Benign

0.019

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.7

PhyloP100

0.99

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.36

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.23

MutPred

0.67

Gain of sheet (P = 0.0477);

MVP

0.10

MPC

0.054

ClinPred

0.23

GERP RS

3.0

Varity_R

0.41

gMVP

0.60

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over