dbSNP rs780149925: PASD1:p.Pro142Thr (chrX-151622942-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_173493.3(PASD1):c.424C>A(p.Pro142Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000183 in 1,094,178 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P142S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Consequence

PASD1
NM_173493.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.299

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:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PASD1	NM_173493.3 link	c.424C>A	p.Pro142Thr	missense_variant	Exon 7 of 16	ENST00000370357.5	NP_775764.2
PASD1	XM_011531102.3 link	c.424C>A	p.Pro142Thr	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.424C>A	p.Pro142Thr	missense_variant	Exon 7 of 16	1	NM_173493.3	ENSP00000359382.4		Q8IV76-1
PASD1	ENST00000464219.1 link	n.562C>A		non_coding_transcript_exon_variant	Exon 7 of 15	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000183

AC:

AN:

1094178

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

359932

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26265

American (AMR)

AF:

0.00

AC:

AN:

34900

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19247

East Asian (EAS)

AF:

0.00

AC:

AN:

30136

South Asian (SAS)

AF:

0.00

AC:

AN:

53398

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40487

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4118

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

839673

Other (OTH)

AF:

0.00

AC:

AN:

45954

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.035

(source)

DANN

Benign

0.36

DEOGEN2

Benign

0.0029

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.28

M_CAP

Benign

0.0057

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.75

PhyloP100

-0.30

PrimateAI

Benign

0.25

PROVEAN

Benign

0.61

REVEL

Benign

0.081

Sift

Benign

0.65

Sift4G

Benign

0.45

Polyphen

0.0

Vest4

0.016

MutPred

0.48

Gain of catalytic residue at F145 (P = 0.1406);

MVP

0.043

MPC

0.030

ClinPred

0.027

GERP RS

-5.5

Varity_R

0.030

gMVP

0.20

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_AL_spliceai

0.21

Position offset: -5

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

Publications

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rs780149925

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over