Genetic Variant PASD1:p.Leu296Ser (chrX-151664164-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173493.3(PASD1):c.887T>C(p.Leu296Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000331 in 1,209,139 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

PASD1
NM_173493.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.42

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05848244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PASD1	NM_173493.3 link	c.887T>C	p.Leu296Ser	missense_variant	Exon 11 of 16	ENST00000370357.5	NP_775764.2
PASD1	XM_011531102.3 link	c.887T>C	p.Leu296Ser	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.887T>C	p.Leu296Ser	missense_variant	Exon 11 of 16	1	NM_173493.3	ENSP00000359382.4		Q8IV76-1
PASD1	ENST00000464219.1 link	n.1025T>C		non_coding_transcript_exon_variant	Exon 11 of 15	2

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

110881

Hom.:

Cov.:

AF XY:

0.0000302

AC XY:

AN XY:

33101

show subpopulations

Gnomad AFR

AF:

0.0000658

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

GnomAD3 exomes

AF:

0.0000218

AC:

AN:

183322

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67780

show subpopulations

Gnomad AFR exome

AF:

0.000304

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000182

AC:

AN:

1098258

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363612

show subpopulations

Gnomad4 AFR exome

AF:

0.0000757

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000180

AC:

AN:

110881

Hom.:

Cov.:

AF XY:

0.0000302

AC XY:

AN XY:

33101

show subpopulations

Gnomad4 AFR

AF:

0.0000658

Gnomad4 AMR

AF:

0.00

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:

0.0000227

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.887T>C (p.L296S) alteration is located in exon 11 (coding exon 10) of the PASD1 gene. This alteration results from a T to C substitution at nucleotide position 887, causing the leucine (L) at amino acid position 296 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

0.23

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.21

DANN

Benign

0.82

DEOGEN2

Benign

0.00089

FATHMM_MKL

Benign

0.0039

LIST_S2

Benign

0.31

M_CAP

Benign

0.0059

MetaRNN

Benign

0.058

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.25

PROVEAN

Benign

0.20

REVEL

Benign

0.048

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0090

Polyphen

0.73

Vest4

0.15

MVP

0.068

MPC

0.073

ClinPred

0.027

GERP RS

-4.7

Varity_R

0.055

gMVP

0.13

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