X-151648698-C-T

Variant names:

• chrX-151648698-C-T
• rs146310228
• NM_173493.3:c.713C>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_173493.3(PASD1):​c.713C>T​(p.Ser238Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000587 in 1,208,732 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 247 hemizygotes in GnomAD. 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: 𝑓 0.00045 (0 hom., 13 hem., cov: 22)
  • Exomes 𝑓: 0.00060 (0 hom. 234 hem.)
• Consequence: PASD1 NM_173493.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.71

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.022760332).
• BP6: Variant X-151648698-C-T is Benign according to our data. Variant chrX-151648698-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2353153.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PASD1	NM_173493.3	c.713C>T	p.Ser238Leu	missense_variant	Exon 9 of 16	ENST00000370357.5	NP_775764.2
PASD1	XM_011531102.3	c.713C>T	p.Ser238Leu	missense_variant	Exon 9 of 16		XP_011529404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PASD1	ENST00000370357.5	c.713C>T	p.Ser238Leu	missense_variant	Exon 9 of 16	1	NM_173493.3	ENSP00000359382.4
PASD1	ENST00000464219.1	n.851C>T		non_coding_transcript_exon_variant	Exon 9 of 15	2

Frequencies

GnomAD3 genomes AF: 0.000449 AC: 50 AN: 111380 Hom.: 0 Cov.: 22 AF XY: 0.000388 AC XY: 13 AN XY: 33546

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000166

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000922

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000442 AC: 80 AN: 180975 Hom.: 0 AF XY: 0.000448 AC XY: 30 AN XY: 66895

Gnomad AFR exome AF: 0.000381

Gnomad AMR exome AF: 0.000183

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000564

Gnomad NFE exome AF: 0.000740

Gnomad OTH exome AF: 0.000445

GnomAD4 exome AF: 0.000601 AC: 660 AN: 1097352 Hom.: 0 Cov.: 31 AF XY: 0.000645 AC XY: 234 AN XY: 362754

Gnomad4 AFR exome AF: 0.000152

Gnomad4 AMR exome AF: 0.000142

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000420

Gnomad4 NFE exome AF: 0.000724

Gnomad4 OTH exome AF: 0.000543

GnomAD4 genome AF: 0.000449 AC: 50 AN: 111380 Hom.: 0 Cov.: 22 AF XY: 0.000388 AC XY: 13 AN XY: 33546

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000166

Gnomad4 NFE AF: 0.000922

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000628 Hom.: 19

Bravo AF: 0.000340

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000346 AC: 1

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.000595 AC: 4

ExAC AF: 0.000469 AC: 57

EpiCase AF: 0.000494

EpiControl AF: 0.000357

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 20, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	0.11
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.029
DANN	Benign	0.86
DEOGEN2	Benign	0.0013	T
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.083
Sift	Uncertain	0.012	D
Sift4G	Benign	0.43	T
Polyphen		0.0050	B
Vest4		0.15
MVP		0.068
MPC		0.027
ClinPred		0.27	T
GERP RS		-5.1
Varity_R		0.056
gMVP		0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs146310228; hg19: chrX-150817170;