8-10765704-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_017884.6(PINX1):c.684C>G(p.Leu228=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00288 in 1,614,002 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (55 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (49 hom.)
• Consequence: PINX1 NM_017884.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0680

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 8-10765704-G-C is Benign according to our data. Variant chr8-10765704-G-C is described in ClinVar as [Benign]. Clinvar id is 789598.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.068 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PINX1	NM_017884.6	c.684C>G	p.Leu228=	synonymous_variant	7/7	ENST00000314787.8
LOC102723313	NR_146188.1	n.341-2696G>C		intron_variant, non_coding_transcript_variant
PINX1	NM_001284356.2	c.*82C>G		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PINX1	ENST00000314787.8	c.684C>G	p.Leu228=	synonymous_variant	7/7	1	NM_017884.6	P2
	ENST00000657150.1	n.174-2696G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2382 AN: 152202 Hom.: 54 Cov.: 33

Gnomad AFR AF: 0.0544

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00628

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: 0.000132

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00386 AC: 962 AN: 249230 Hom.: 19 AF XY: 0.00299 AC XY: 404 AN XY: 135218

Gnomad AFR exome AF: 0.0560

Gnomad AMR exome AF: 0.00200

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.00154 AC: 2253 AN: 1461682 Hom.: 49 Cov.: 33 AF XY: 0.00132 AC XY: 961 AN XY: 727130

Gnomad4 AFR exome AF: 0.0558

Gnomad4 AMR exome AF: 0.00250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000711

Gnomad4 OTH exome AF: 0.00298

GnomAD4 genome AF: 0.0157 AC: 2394 AN: 152320 Hom.: 55 Cov.: 33 AF XY: 0.0147 AC XY: 1095 AN XY: 74476

Gnomad4 AFR AF: 0.0546

Gnomad4 AMR AF: 0.00627

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00992

Alfa AF: 0.00409 Hom.: 5

Bravo AF: 0.0179

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 20, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.42
Dann	Benign	0.52

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: rs17152322; hg19: chr8-10623214;