chrX-151604680-A-C

Variant names:

• chrX-151604680-A-C
• NM_173493.3:c.63A>C

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.63A>C​(p.Leu21Phe) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: PASD1 NM_173493.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.977
• 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=0.06995964).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PASD1	NM_173493.3	c.63A>C	p.Leu21Phe	missense_variant	Exon 3 of 16	ENST00000370357.5	NP_775764.2
PASD1	XM_011531102.3	c.63A>C	p.Leu21Phe	missense_variant	Exon 3 of 16		XP_011529404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PASD1	ENST00000370357.5	c.63A>C	p.Leu21Phe	missense_variant	Exon 3 of 16	1	NM_173493.3	ENSP00000359382.4
PASD1	ENST00000464219.1	n.201A>C		non_coding_transcript_exon_variant	Exon 3 of 15	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.63A>C (p.L21F) alteration is located in exon 3 (coding exon 2) of the PASD1 gene. This alteration results from a A to C substitution at nucleotide position 63, causing the leucine (L) at amino acid position 21 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	0.13
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.85
DANN	Benign	0.84
DEOGEN2	Benign	0.0053	T
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.98
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.12
Sift	Benign	0.059	T
Sift4G	Benign	0.23	T
Polyphen		0.069	B
Vest4		0.17
MutPred		0.32		Loss of catalytic residue at L21 (P = 0.003);
MVP		0.093
MPC		0.17
ClinPred		0.094	T
GERP RS		-8.5
Varity_R		0.073
gMVP		0.067
Mutation Taster		=99/1	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

hg19: chrX-150773152;