chrX-151620960-C-T

Position:

• chrX-151620960-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_173493.3(PASD1):​c.238C>T​(p.Leu80Phe) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: PASD1 NM_173493.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0110

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041163296).
• BP6: Variant X-151620960-C-T is Benign according to our data. Variant chrX-151620960-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2300634.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PASD1	NM_173493.3	c.238C>T	p.Leu80Phe	missense_variant	5/16	ENST00000370357.5
PASD1	XM_011531102.3	c.238C>T	p.Leu80Phe	missense_variant	5/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PASD1	ENST00000370357.5	c.238C>T	p.Leu80Phe	missense_variant	5/16	1	NM_173493.3	P1
PASD1	ENST00000464219.1	n.376C>T		non_coding_transcript_exon_variant	5/15	2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 22

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.4
DANN	Benign	0.91
DEOGEN2	Benign	0.0012	T
FATHMM_MKL	Benign	0.0028	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.085	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	3.7	N
REVEL	Benign	0.088
Sift	Benign	0.22	T
Sift4G	Uncertain	0.022	D
Polyphen		0.56	P
Vest4		0.12
MutPred		0.46		Loss of ubiquitination at K75 (P = 0.0683);
MVP		0.093
MPC		0.036
ClinPred		0.16	T
GERP RS		-1.4
Varity_R		0.054
gMVP		0.19

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-150789432;