Genetic Variant PINX1:c.394+768G>A (chr8-10825384-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.409

Variant links:

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]

PINX1 links:

MIR1322 (HGNC:35374): (microRNA 1322) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR1322 links:

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ACMG classification

Classification made for transcript

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	Effect	Exon rank	MANE	Protein	UniProt
PINX1	NM_017884.6 link	c.394+768G>A	intron_variant	Intron 5 of 6	ENST00000314787.8	NP_060354.4	Q96BK5-1
PINX1	NM_001284356.2 link	c.394+768G>A	intron_variant	Intron 5 of 5		NP_001271285.1	Q96BK5-2
MIR1322	NR_031711.1 link	n.60G>A	non_coding_transcript_exon_variant	Exon 1 of 1
MIR1322	unassigned_transcript_1451	n.10G>A	non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PINX1	ENST00000314787.8 link	c.394+768G>A		intron_variant	Intron 5 of 6	1	NM_017884.6	ENSP00000318966.3		Q96BK5-1
PINX1	ENST00000554914.1 link	c.394+768G>A		intron_variant	Intron 5 of 5	2		ENSP00000451145.1		A0A0A6YYK5

Frequencies

GnomAD3 genomes

AF:

0.0622

AC:

9460

AN:

152156

Hom.:

1010

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.00610

AC XY:

1328

AN XY:

217724

show subpopulations

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.:

AF XY:

0.0597

AC XY:

4447

AN XY:

74468

show subpopulations

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:

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over