dbSNP rs768226760: PASD1:p.Lys7Gln (chrX-151601572-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173493.3(PASD1):c.19A>C(p.Lys7Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,998 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. 16/21 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. K7N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

PASD1
NM_173493.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.689

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1341263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PASD1	NM_173493.3 link	c.19A>C	p.Lys7Gln	missense_variant	Exon 2 of 16	ENST00000370357.5	NP_775764.2
PASD1	XM_011531102.3 link	c.19A>C	p.Lys7Gln	missense_variant	Exon 2 of 16		XP_011529404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PASD1	ENST00000370357.5 link	c.19A>C	p.Lys7Gln	missense_variant	Exon 2 of 16	1	NM_173493.3	ENSP00000359382.4		Q8IV76-1
PASD1	ENST00000464219.1 link	n.157A>C		non_coding_transcript_exon_variant	Exon 2 of 15	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000549

AC:

AN:

182200

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.12e-7

AC:

AN:

1096998

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362362

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

26363

American (AMR)

AF:

0.00

AC:

AN:

35163

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19370

East Asian (EAS)

AF:

0.00

AC:

AN:

30184

South Asian (SAS)

AF:

0.00

AC:

AN:

54015

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40524

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

841198

Other (OTH)

AF:

0.00

AC:

AN:

46051

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

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

0.19

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.68

CADD

Benign

1.0

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.00096

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.36

M_CAP

Benign

0.023

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.46

PhyloP100

0.69

PrimateAI

Benign

0.31

PROVEAN

Benign

0.86

REVEL

Benign

0.17

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.025

Polyphen

0.99

Vest4

0.29

MutPred

0.28

Loss of sheet (P = 0.0228);

MVP

0.068

MPC

0.12

ClinPred

0.16

GERP RS

-5.9

Varity_R

0.12

gMVP

0.25

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over