X-151621523-G-A

Variant names:

• chrX-151621523-G-A
• rs751590635
• NM_173493.3:c.349G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_173493.3(PASD1):​c.349G>A​(p.Val117Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000598 in 1,204,814 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 28 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 1 hem., cov: 21)
  • Exomes 𝑓: 0.000061 (0 hom. 27 hem.)
• Consequence: PASD1 NM_173493.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.19
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0290505).
• BS2: High Hemizygotes in GnomAdExome4 at 27 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PASD1	NM_173493.3	c.349G>A	p.Val117Ile	missense_variant	Exon 6 of 16	ENST00000370357.5	NP_775764.2
PASD1	XM_011531102.3	c.349G>A	p.Val117Ile	missense_variant	Exon 6 of 16		XP_011529404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PASD1	ENST00000370357.5	c.349G>A	p.Val117Ile	missense_variant	Exon 6 of 16	1	NM_173493.3	ENSP00000359382.4
PASD1	ENST00000464219.1	n.487G>A		non_coding_transcript_exon_variant	Exon 6 of 15	2

Frequencies

GnomAD3 genomes AF: 0.0000448 AC: 5 AN: 111596 Hom.: 0 Cov.: 21

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000942

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000451 AC: 8 AN: 177195 AF XY: 0.0000804

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000749

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000613 AC: 67 AN: 1093165 Hom.: 0 Cov.: 28 AF XY: 0.0000751 AC XY: 27 AN XY: 359389

African (AFR) AF: 0.00 AC: 0 AN: 26234

American (AMR) AF: 0.00 AC: 0 AN: 34697

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19272

East Asian (EAS) AF: 0.00 AC: 0 AN: 30051

South Asian (SAS) AF: 0.000151 AC: 8 AN: 52969

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40419

Middle Eastern (MID) AF: 0.000251 AC: 1 AN: 3987

European-Non Finnish (NFE) AF: 0.0000631 AC: 53 AN: 839631

Other (OTH) AF: 0.000109 AC: 5 AN: 45905

GnomAD4 genome AF: 0.0000448 AC: 5 AN: 111649 Hom.: 0 Cov.: 21 AF XY: 0.0000295 AC XY: 1 AN XY: 33843

African (AFR) AF: 0.00 AC: 0 AN: 30814

American (AMR) AF: 0.00 AC: 0 AN: 10462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3546

South Asian (SAS) AF: 0.00 AC: 0 AN: 2605

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6051

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.0000942 AC: 5 AN: 53098

Other (OTH) AF: 0.00 AC: 0 AN: 1522

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.0000741 AC: 9

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 31, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.349G>A (p.V117I) alteration is located in exon 6 (coding exon 5) of the PASD1 gene. This alteration results from a G to A substitution at nucleotide position 349, causing the valine (V) at amino acid position 117 to be replaced by an isoleucine (I). 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	-0.60	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.0030
DANN	Benign	0.72
DEOGEN2	Benign	0.00091	T
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-1.2
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.25	N
REVEL	Benign	0.023
Sift	Benign	0.11	T
Sift4G	Benign	0.065	T
Polyphen		0.11	B
Vest4		0.028
MVP		0.043
MPC		0.045
ClinPred		0.027	T
GERP RS		-8.0
Varity_R		0.034
gMVP		0.11
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs751590635; hg19: chrX-150789995;