X-151664236-T-G

Variant names:

• chrX-151664236-T-G
• NM_173493.3:c.959T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173493.3(PASD1):​c.959T>G​(p.Met320Arg) 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 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: -0.783

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12010917).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PASD1	NM_173493.3	c.959T>G	p.Met320Arg	missense_variant	Exon 11 of 16	ENST00000370357.5	NP_775764.2
PASD1	XM_011531102.3	c.959T>G	p.Met320Arg	missense_variant	Exon 11 of 16		XP_011529404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PASD1	ENST00000370357.5	c.959T>G	p.Met320Arg	missense_variant	Exon 11 of 16	1	NM_173493.3	ENSP00000359382.4
PASD1	ENST00000464219.1	n.1097T>G		non_coding_transcript_exon_variant	Exon 11 of 15	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.959T>G (p.M320R) alteration is located in exon 11 (coding exon 10) of the PASD1 gene. This alteration results from a T to G substitution at nucleotide position 959, causing the methionine (M) at amino acid position 320 to be replaced by an arginine (R). 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	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.8
DANN	Benign	0.63
DEOGEN2	Benign	0.00085	T
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.16
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.012	D
Polyphen		0.92	P
Vest4		0.14
MutPred		0.093		Gain of loop (P = 0.0502);
MVP		0.25
MPC		0.045
ClinPred		0.13	T
GERP RS		-1.6
Varity_R		0.32
gMVP		0.078

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-150832708;