Variant chrX-151622998-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173493.3(PASD1):c.480T>G(p.Cys160Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000893 in 111,928 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Consequence

PASD1
NM_173493.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.28

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:

PASD1 (HGNC:):

PASD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1135298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PASD1	NM_173493.3 linkuse as main transcript	c.480T>G	p.Cys160Trp	missense_variant	7/16	ENST00000370357.5	NP_775764.2
PASD1	XM_011531102.3 linkuse as main transcript	c.480T>G	p.Cys160Trp	missense_variant	7/16		XP_011529404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PASD1	ENST00000370357.5 linkuse as main transcript	c.480T>G	p.Cys160Trp	missense_variant	7/16	1	NM_173493.3	ENSP00000359382.4		Q8IV76-1
PASD1	ENST00000464219.1 linkuse as main transcript	n.618T>G		non_coding_transcript_exon_variant	7/15	2

Frequencies

GnomAD3 genomes

AF:

0.00000893

AC:

AN:

111928

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34070

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000950

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

AF:

0.00000893

AC:

AN:

111928

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34070

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000950

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 11, 2023

The c.480T>G (p.C160W) alteration is located in exon 7 (coding exon 6) of the PASD1 gene. This alteration results from a T to G substitution at nucleotide position 480, causing the cysteine (C) at amino acid position 160 to be replaced by a tryptophan (W). 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

0.19

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.3

DANN

Benign

0.72

DEOGEN2

Benign

0.0019

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.34

M_CAP

Benign

0.011

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.68

REVEL

Benign

0.18

Sift

Benign

0.043

Sift4G

Uncertain

0.026

Polyphen

0.90

Vest4

0.13

MutPred

0.56

Gain of sheet (P = 0.1945);

MVP

0.043

MPC

0.054

ClinPred

0.10

GERP RS

-2.6

Varity_R

0.13

gMVP

0.27

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over