8-10825384-C-T

Position:

• chr8-10825384-C-T

Variant summary

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

The NM_017884.6(PINX1):​c.394+768G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0234 in 534,734 control chromosomes in the GnomAD database, including 1,259 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 0.062 (1013 hom., cov: 33)
  • Exomes 𝑓: 0.0079 (246 hom.)
• Consequence: PINX1 NM_017884.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409

Genes affected

PINX1 (HGNC:30046): (PIN2 (TERF1) interacting telomerase inhibitor 1) Enables telomerase RNA binding activity and telomerase inhibitor activity. Involved in several processes, including negative regulation of DNA biosynthetic process; positive regulation of protein localization to nucleolus; and protein localization to organelle. Acts upstream of or within telomere maintenance via telomerase. Located in several cellular components, including chromosomal region; nuclear lumen; and spindle. [provided by Alliance of Genome Resources, Apr 2022]

MIR1322 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PINX1	NM_017884.6	c.394+768G>A		intron_variant		ENST00000314787.8	NP_060354.4
PINX1	NM_001284356.2	c.394+768G>A		intron_variant			NP_001271285.1
MIR1322	NR_031711.1	n.60G>A		non_coding_transcript_exon_variant	1/1
MIR1322	unassigned_transcript_1451	n.10G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PINX1	ENST00000314787.8	c.394+768G>A		intron_variant		1	NM_017884.6	ENSP00000318966.3
PINX1	ENST00000554914.1	c.394+768G>A		intron_variant		2		ENSP00000451145.1

Frequencies

GnomAD3 genomes AF: 0.0622 AC: 9460 AN: 152156 Hom.: 1010 Cov.: 33

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0242

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.0344

GnomAD3 exomes AF: 0.0159 AC: 3921 AN: 246698 Hom.: 381 AF XY: 0.0122 AC XY: 1640 AN XY: 134278

Gnomad AFR exome AF: 0.221

Gnomad AMR exome AF: 0.0109

Gnomad ASJ exome AF: 0.000299

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000669

Gnomad OTH exome AF: 0.00761

GnomAD4 exome AF: 0.00791 AC: 3027 AN: 382460 Hom.: 246 Cov.: 0 AF XY: 0.00610 AC XY: 1328 AN XY: 217724

Gnomad4 AFR exome AF: 0.214

Gnomad4 AMR exome AF: 0.0110

Gnomad4 ASJ exome AF: 0.000170

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000494

Gnomad4 FIN exome AF: 0.0000309

Gnomad4 NFE exome AF: 0.000625

Gnomad4 OTH exome AF: 0.0120

GnomAD4 genome AF: 0.0622 AC: 9470 AN: 152274 Hom.: 1013 Cov.: 33 AF XY: 0.0597 AC XY: 4447 AN XY: 74468

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.0241

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000750

Gnomad4 OTH AF: 0.0341

Alfa AF: 0.0272 Hom.: 196

Bravo AF: 0.0704

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.5
DANN	Benign	0.65

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: rs59878596; hg19: chr8-10682894;