Genetic Variant PASD1:p.Met320Val (chrX-151664235-A-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M320R) has been classified as Uncertain significance.

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

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -1.18

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: Benign. The variant received -9 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 Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 2661644.

BS2

High Hemizygotes in GnomAd4 at 9 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173493.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PASD1	NM_173493.3	MANE Select	c.958A>G	p.Met320Val	missense	Exon 11 of 16	NP_775764.2	Q8IV76-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PASD1	ENST00000370357.5	TSL:1 MANE Select	c.958A>G	p.Met320Val	missense	Exon 11 of 16	ENSP00000359382.4	Q8IV76-1
	PASD1	ENST00000464219.1	TSL:2	n.1096A>G		non_coding_transcript_exon	Exon 11 of 15

Frequencies

GnomAD3 genomes

AF:

0.000318

AC:

AN:

110167

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000928

AC:

AN:

183279

AF XY:

0.000118

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 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

African (AFR)

AF:

0.00

AC:

AN:

26360

American (AMR)

AF:

0.000542

AC:

AN:

35033

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19355

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30206

South Asian (SAS)

AF:

0.000148

AC:

AN:

54046

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40518

Middle Eastern (MID)

AF:

0.000248

AC:

AN:

4030

European-Non Finnish (NFE)

AF:

0.000156

AC:

130

AN:

833792

Other (OTH)

AF:

0.000306

AC:

AN:

45766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000318

AC:

AN:

110226

Hom.:

Cov.:

AF XY:

0.000273

AC XY:

AN XY:

33016

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30417

American (AMR)

AF:

0.00239

AC:

AN:

10472

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2627

East Asian (EAS)

AF:

0.000864

AC:

AN:

3473

South Asian (SAS)

AF:

0.00

AC:

AN:

2495

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6085

Middle Eastern (MID)

AF:

0.00

AC:

AN:

197

European-Non Finnish (NFE)

AF:

0.0000956

AC:

AN:

52292

Other (OTH)

AF:

0.00134

AC:

AN:

1492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00473

Hom.:

104

Bravo

AF:

0.000608

ExAC

AF:

0.0000909

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0040

(source)

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

PhyloP100

-1.2

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

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over