rs5924658

Positions:

• chrX-151648622-C-G
• chrX-151648622-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173493.3(PASD1):​c.637C>G​(p.Gln213Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,207,244 control chromosomes in the GnomAD database, including 28,515 homozygotes. There are 100,240 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.20 (2041 hom., 6303 hem., cov: 22)
  • Exomes 𝑓: 0.26 (26474 hom. 93937 hem.)
• Consequence: PASD1 NM_173493.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0056649745).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PASD1	NM_173493.3	c.637C>G	p.Gln213Glu	missense_variant	9/16	ENST00000370357.5
PASD1	XM_011531102.3	c.637C>G	p.Gln213Glu	missense_variant	9/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PASD1	ENST00000370357.5	c.637C>G	p.Gln213Glu	missense_variant	9/16	1	NM_173493.3	P1
PASD1	ENST00000464219.1	n.775C>G		non_coding_transcript_exon_variant	9/15	2

Frequencies

GnomAD3 genomes AF: 0.197 AC: 21810 AN: 110911 Hom.: 2042 Cov.: 22 AF XY: 0.190 AC XY: 6304 AN XY: 33145

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.0272

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.289

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.227

GnomAD3 exomes AF: 0.230 AC: 41663 AN: 180824 Hom.: 3485 AF XY: 0.236 AC XY: 15735 AN XY: 66674

Gnomad AFR exome AF: 0.0354

Gnomad AMR exome AF: 0.248

Gnomad ASJ exome AF: 0.308

Gnomad EAS exome AF: 0.0175

Gnomad SAS exome AF: 0.186

Gnomad FIN exome AF: 0.311

Gnomad NFE exome AF: 0.280

Gnomad OTH exome AF: 0.251

GnomAD4 exome AF: 0.261 AC: 286135 AN: 1096278 Hom.: 26474 Cov.: 30 AF XY: 0.260 AC XY: 93937 AN XY: 361972

Gnomad4 AFR exome AF: 0.0342

Gnomad4 AMR exome AF: 0.243

Gnomad4 ASJ exome AF: 0.308

Gnomad4 EAS exome AF: 0.0352

Gnomad4 SAS exome AF: 0.186

Gnomad4 FIN exome AF: 0.314

Gnomad4 NFE exome AF: 0.279

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.196 AC: 21798 AN: 110966 Hom.: 2041 Cov.: 22 AF XY: 0.190 AC XY: 6303 AN XY: 33210

Gnomad4 AFR AF: 0.0408

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.0276

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.224

Alfa AF: 0.243 Hom.: 2198

Bravo AF: 0.187

TwinsUK AF: 0.280 AC: 1040

ALSPAC AF: 0.286 AC: 827

ESP6500AA AF: 0.0415 AC: 159

ESP6500EA AF: 0.277 AC: 1861

ExAC AF: 0.227 AC: 27534

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.2
DANN	Benign	0.94
DEOGEN2	Benign	0.0014	T
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.0057	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.070
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.027	D
Polyphen		0.74	P
Vest4		0.049
MPC		0.12
ClinPred		0.0089	T
GERP RS		1.1
Varity_R		0.087
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5924658; hg19: chrX-150817094; COSMIC: COSV64855324;