chrX-151625491-C-T

Variant names:

• chrX-151625491-C-T
• rs1362497997
• NM_173493.3:c.590C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_173493.3(PASD1):​c.590C>T​(p.Thr197Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,207,820 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000048 (0 hom. 19 hem.)
• Consequence: PASD1 NM_173493.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.40
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.035190135).
• BP6: Variant X-151625491-C-T is Benign according to our data. Variant chrX-151625491-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3885820.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PASD1	NM_173493.3	c.590C>T	p.Thr197Ile	missense_variant	Exon 8 of 16	ENST00000370357.5	NP_775764.2
PASD1	XM_011531102.3	c.590C>T	p.Thr197Ile	missense_variant	Exon 8 of 16		XP_011529404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PASD1	ENST00000370357.5	c.590C>T	p.Thr197Ile	missense_variant	Exon 8 of 16	1	NM_173493.3	ENSP00000359382.4
PASD1	ENST00000464219.1	n.728C>T		non_coding_transcript_exon_variant	Exon 8 of 15	2

Frequencies

GnomAD3 genomes AF: 0.00000892 AC: 1 AN: 112107 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

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: 0.000661

GnomAD2 exomes AF: 0.0000110 AC: 2 AN: 181255 AF XY: 0.0000152

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: 0.0000246

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000484 AC: 53 AN: 1095713 Hom.: 0 Cov.: 28 AF XY: 0.0000526 AC XY: 19 AN XY: 361205

African (AFR) AF: 0.00 AC: 0 AN: 26349

American (AMR) AF: 0.00 AC: 0 AN: 35123

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19349

East Asian (EAS) AF: 0.00 AC: 0 AN: 30137

South Asian (SAS) AF: 0.00 AC: 0 AN: 53643

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 0.0000607 AC: 51 AN: 840468

Other (OTH) AF: 0.0000435 AC: 2 AN: 46010

GnomAD4 genome AF: 0.00000892 AC: 1 AN: 112107 Hom.: 0 Cov.: 23 AF XY: 0.0000292 AC XY: 1 AN XY: 34301

African (AFR) AF: 0.00 AC: 0 AN: 30853

American (AMR) AF: 0.00 AC: 0 AN: 10469

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2643

East Asian (EAS) AF: 0.00 AC: 0 AN: 3597

South Asian (SAS) AF: 0.00 AC: 0 AN: 2706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6081

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53320

Other (OTH) AF: 0.000661 AC: 1 AN: 1513

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 12, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.0010
DANN	Benign	0.21
DEOGEN2	Benign	0.0011	T
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N
PhyloP100		-3.4
PrimateAI	Benign	0.30	T
PROVEAN	Benign	2.0	N
REVEL	Benign	0.11
Sift	Benign	0.97	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.069
MutPred		0.52		Loss of glycosylation at T197 (P = 0.0192);
MVP		0.043
MPC		0.029
ClinPred		0.021	T
GERP RS		-5.6
Varity_R		0.027
gMVP		0.36
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1362497997; hg19: chrX-150793963;