NM_173493.3:c.590C>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173493.3(PASD1):​c.590C>A​(p.Thr197Lys) 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. 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. T197I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: PASD1 NM_173493.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.40
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060826898).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PASD1	NM_173493.3	c.590C>A	p.Thr197Lys	missense_variant	Exon 8 of 16	ENST00000370357.5	NP_775764.2
PASD1	XM_011531102.3	c.590C>A	p.Thr197Lys	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>A	p.Thr197Lys	missense_variant	Exon 8 of 16	1	NM_173493.3	ENSP00000359382.4
PASD1	ENST00000464219.1	n.728C>A		non_coding_transcript_exon_variant	Exon 8 of 15	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.010
DANN	Benign	0.50
DEOGEN2	Benign	0.0017	T
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		-3.4
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.14
Sift	Benign	0.056	T
Sift4G	Benign	0.16	T
Polyphen		0.0070	B
Vest4		0.16
MutPred		0.48		Gain of ubiquitination at T197 (P = 0.0162);
MVP		0.043
MPC		0.085
ClinPred		0.19	T
GERP RS		-5.6
Varity_R		0.099
gMVP		0.43
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;