chrX-151601572-A-C

Variant names:

• chrX-151601572-A-C
• rs768226760
• NM_173493.3:c.19A>C

Variant summary

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

The NM_173493.3(PASD1):​c.19A>C​(p.Lys7Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,998 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. K7E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: PASD1 NM_173493.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.689

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=0.1341263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PASD1	NM_173493.3	c.19A>C	p.Lys7Gln	missense_variant	Exon 2 of 16	ENST00000370357.5	NP_775764.2
PASD1	XM_011531102.3	c.19A>C	p.Lys7Gln	missense_variant	Exon 2 of 16		XP_011529404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PASD1	ENST00000370357.5	c.19A>C	p.Lys7Gln	missense_variant	Exon 2 of 16	1	NM_173493.3	ENSP00000359382.4
PASD1	ENST00000464219.1	n.157A>C		non_coding_transcript_exon_variant	Exon 2 of 15	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.00000549 AC: 1 AN: 182200 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 66660

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1096998 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 362362

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.0
DANN	Benign	0.77
DEOGEN2	Benign	0.00096	T
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.46	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.86	N
REVEL	Benign	0.17
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.025	D
Polyphen		0.99	D
Vest4		0.29
MutPred		0.28		Loss of sheet (P = 0.0228);
MVP		0.068
MPC		0.12
ClinPred		0.16	T
GERP RS		-5.9
Varity_R		0.12
gMVP		0.25

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

LitVar

Other links and lift over

dbSNP: rs768226760; hg19: chrX-150770044;