chrX-151623027-T-C

Variant names:

• chrX-151623027-T-C
• rs766579845
• NM_173493.3:c.509T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_173493.3(PASD1):​c.509T>C​(p.Val170Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000019 in 1,207,644 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000020 (0 hom. 5 hem.)
• Consequence: PASD1 NM_173493.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.75
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.28463382).
• BS2: High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PASD1	NM_173493.3	c.509T>C	p.Val170Ala	missense_variant	Exon 7 of 16	ENST00000370357.5	NP_775764.2
PASD1	XM_011531102.3	c.509T>C	p.Val170Ala	missense_variant	Exon 7 of 16		XP_011529404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PASD1	ENST00000370357.5	c.509T>C	p.Val170Ala	missense_variant	Exon 7 of 16	1	NM_173493.3	ENSP00000359382.4
PASD1	ENST00000464219.1	n.647T>C		non_coding_transcript_exon_variant	Exon 7 of 15	2

Frequencies

GnomAD3 genomes AF: 0.00000896 AC: 1 AN: 111652 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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000330 AC: 6 AN: 181979 AF XY: 0.0000301

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: 0.0000737

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000201 AC: 22 AN: 1095992 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 5 AN XY: 361554

African (AFR) AF: 0.00 AC: 0 AN: 26356

American (AMR) AF: 0.00 AC: 0 AN: 35129

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19362

East Asian (EAS) AF: 0.00 AC: 0 AN: 30167

South Asian (SAS) AF: 0.00 AC: 0 AN: 53940

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40510

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.0000262 AC: 22 AN: 840365

Other (OTH) AF: 0.00 AC: 0 AN: 46032

GnomAD4 genome AF: 0.00000896 AC: 1 AN: 111652 Hom.: 0 Cov.: 23 AF XY: 0.0000296 AC XY: 1 AN XY: 33816

African (AFR) AF: 0.00 AC: 0 AN: 30677

American (AMR) AF: 0.00 AC: 0 AN: 10478

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3549

South Asian (SAS) AF: 0.00 AC: 0 AN: 2639

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53161

Other (OTH) AF: 0.00 AC: 0 AN: 1496

Alfa AF: 0.0000868 Hom.: 1

Bravo AF: 0.0000189

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.00

EpiControl AF: 0.0000600

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.509T>C (p.V170A) alteration is located in exon 7 (coding exon 6) of the PASD1 gene. This alteration results from a T to C substitution at nucleotide position 509, causing the valine (V) at amino acid position 170 to be replaced by an alanine (A). 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	0.27
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Benign	0.065	T
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.8
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.018	D
Polyphen		0.89	P
Vest4		0.47
MVP		0.22
MPC		0.16
ClinPred		0.29	T
GERP RS		2.8
Varity_R		0.19
gMVP		0.49
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs766579845; hg19: chrX-150791499;