Genetic Variant PASD1:p.Met320Val (chrX-151664235-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_173493.3(PASD1):c.958A>G(p.Met320Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000173 in 1,199,332 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 67 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. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., 9 hem., cov: 23)

Exomes 𝑓: 0.00016 ( 0 hom. 58 hem. )

Consequence

PASD1
NM_173493.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.18

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007728517).

BP6

Variant X-151664235-A-G is Benign according to our data. Variant chrX-151664235-A-G is described in ClinVar as [Benign]. Clinvar id is 2661644.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PASD1	NM_173493.3 link	c.958A>G	p.Met320Val	missense_variant	Exon 11 of 16	ENST00000370357.5	NP_775764.2
PASD1	XM_011531102.3 link	c.958A>G	p.Met320Val	missense_variant	Exon 11 of 16		XP_011529404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PASD1	ENST00000370357.5 link	c.958A>G	p.Met320Val	missense_variant	Exon 11 of 16	1	NM_173493.3	ENSP00000359382.4		Q8IV76-1
PASD1	ENST00000464219.1 link	n.1096A>G		non_coding_transcript_exon_variant	Exon 11 of 15	2

Frequencies

GnomAD3 genomes

AF:

0.000318

AC:

AN:

110167

Hom.:

Cov.:

AF XY:

0.000273

AC XY:

AN XY:

32951

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00239

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000861

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000956

Gnomad OTH

AF:

0.00136

GnomAD3 exomes

AF:

0.0000928

AC:

AN:

183279

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

67757

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000722

Gnomad SAS exome

AF:

0.000157

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000979

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000159

AC:

173

AN:

1089106

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

AN XY:

361794

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000542

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.000148

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000156

Gnomad4 OTH exome

AF:

0.000306

GnomAD4 genome

AF:

0.000318

AC:

AN:

110226

Hom.:

Cov.:

AF XY:

0.000273

AC XY:

AN XY:

33016

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00239

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000864

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000956

Gnomad4 OTH

AF:

0.00134

Alfa

AF:

0.00535

Hom.:

Bravo

AF:

0.000608

ExAC

AF:

0.0000909

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PASD1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0040

DANN

Benign

0.43

DEOGEN2

Benign

0.0012

FATHMM_MKL

Benign

0.00049

LIST_S2

Benign

0.38

M_CAP

Benign

0.0052

MetaRNN

Benign

0.0077

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.84

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.61

REVEL

Benign

0.056

Sift

Benign

0.24

Sift4G

Benign

0.94

Polyphen

0.010

Vest4

0.013

MVP

0.13

MPC

0.028

ClinPred

0.018

GERP RS

-4.5

Varity_R

0.049

gMVP

0.043

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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