chrX-151622942-C-G

Variant names:

• chrX-151622942-C-G
• rs780149925
• NM_173493.3:c.424C>G

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.424C>G​(p.Pro142Ala) 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. P142S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: PASD1 NM_173493.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299
• 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=0.046091765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PASD1	NM_173493.3	c.424C>G	p.Pro142Ala	missense_variant	Exon 7 of 16	ENST00000370357.5	NP_775764.2
PASD1	XM_011531102.3	c.424C>G	p.Pro142Ala	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.424C>G	p.Pro142Ala	missense_variant	Exon 7 of 16	1	NM_173493.3	ENSP00000359382.4
PASD1	ENST00000464219.1	n.562C>G		non_coding_transcript_exon_variant	Exon 7 of 15	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.0080
DANN	Benign	0.34
DEOGEN2	Benign	0.0057	T
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.30
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.13
Sift	Benign	0.78	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.037
MutPred		0.51		Gain of catalytic residue at P142 (P = 0.0179);
MVP		0.043
MPC		0.028
ClinPred		0.018	T
GERP RS		-5.5
Varity_R		0.018
gMVP		0.11
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs780149925; hg19: chrX-150791414;