rs2013561916

Variant names:

• chrX-151611731-C-T
• rs2013561916
• NM_173493.3:c.185C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173493.3(PASD1):​c.185C>T​(p.Ser62Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: PASD1 NM_173493.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00400
• 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: 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=0.258426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PASD1	NM_173493.3	c.185C>T	p.Ser62Phe	missense_variant	Exon 4 of 16	ENST00000370357.5	NP_775764.2
PASD1	XM_011531102.3	c.185C>T	p.Ser62Phe	missense_variant	Exon 4 of 16		XP_011529404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PASD1	ENST00000370357.5	c.185C>T	p.Ser62Phe	missense_variant	Exon 4 of 16	1	NM_173493.3	ENSP00000359382.4
PASD1	ENST00000464219.1	n.323C>T		non_coding_transcript_exon_variant	Exon 4 of 15	2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.185C>T (p.S62F) alteration is located in exon 4 (coding exon 3) of the PASD1 gene. This alteration results from a C to T substitution at nucleotide position 185, causing the serine (S) at amino acid position 62 to be replaced by a phenylalanine (F). 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	0.32
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	5.9
DANN	Benign	0.92
DEOGEN2	Benign	0.054	T
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.0040
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-4.4	D
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.29
MutPred		0.54		Gain of helix (P = 0.2294);
MVP		0.043
MPC		0.041
ClinPred		0.95	D
GERP RS		-4.5
Varity_R		0.22
gMVP		0.57
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs2013561916; hg19: chrX-150780203;