rs12190911

Positions:

• chr6-36410710-A-G

Variant summary

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

The NM_152990.4(PXT1):​c.170-10126T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,112 control chromosomes in the GnomAD database, including 4,176 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4176 hom., cov: 32)
• Consequence: PXT1 NM_152990.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396

Genes affected

PXT1 (HGNC:18312): (peroxisomal testis enriched protein 1) Predicted to be involved in positive regulation of apoptotic process. Predicted to act upstream of or within spermatogenesis. Predicted to be active in nucleus and peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXT1	NM_152990.4	c.170-10126T>C		intron_variant		ENST00000454782.3	NP_694535.2
PXT1	XM_011514400.3	c.185-10126T>C		intron_variant			XP_011512702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PXT1	ENST00000454782.3	c.170-10126T>C		intron_variant		1	NM_152990.4	ENSP00000419944.1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34919 AN: 151994 Hom.: 4173 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.235

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.230 AC: 34947 AN: 152112 Hom.: 4176 Cov.: 32 AF XY: 0.232 AC XY: 17240 AN XY: 74358

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.236

Alfa AF: 0.233 Hom.: 2072

Bravo AF: 0.225

Asia WGS AF: 0.266 AC: 927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.37

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: rs12190911; hg19: chr6-36378487;