Variant 15-64818018-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001286496.2(PIF1):c.1602C>T(p.Thr534Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00359 in 1,613,470 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 28 hom. )

Consequence

PIF1
NM_001286496.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.08

Variant links:

Genes affected

PIF1 (HGNC:26220): (PIF1 5'-to-3' DNA helicase) This gene encodes a DNA-dependent adenosine triphosphate (ATP)-metabolizing enzyme that functions as a 5' to 3' DNA helicase. The encoded protein can resolve G-quadruplex structures and RNA-DNA hybrids at the ends of chromosomes. It also prevents telomere elongation by inhibiting the actions of telomerase. Alternative splicing and the use of alternative start codons results in multiple isoforms that are differentially localized to either the mitochondria or the nucleus. [provided by RefSeq, Nov 2013]

PIF1 links:

PIF1 (HGNC:):

PIF1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 15-64818018-G-A is Benign according to our data. Variant chr15-64818018-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2645444.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.08 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIF1	NM_001286496.2 linkuse as main transcript	c.1602C>T	p.Thr534Thr	synonymous_variant	11/13	ENST00000559239.2	NP_001273425.1	Q9H611-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIF1	ENST00000559239.2 linkuse as main transcript	c.1602C>T	p.Thr534Thr	synonymous_variant	11/13	1	NM_001286496.2	ENSP00000452792.1		Q9H611-1

Frequencies

GnomAD3 genomes

AF:

0.00362

AC:

551

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00942

Gnomad ASJ

AF:

0.0306

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00347

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00465

AC:

1153

AN:

247738

Hom.:

AF XY:

0.00480

AC XY:

645

AN XY:

134314

show subpopulations

Gnomad AFR exome

AF:

0.000885

Gnomad AMR exome

AF:

0.00647

Gnomad ASJ exome

AF:

0.0311

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00220

Gnomad FIN exome

AF:

0.000806

Gnomad NFE exome

AF:

0.00416

Gnomad OTH exome

AF:

0.00948

GnomAD4 exome

AF:

0.00358

AC:

5235

AN:

1461202

Hom.:

Cov.:

AF XY:

0.00368

AC XY:

2678

AN XY:

726878

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.00672

Gnomad4 ASJ exome

AF:

0.0299

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00263

Gnomad4 FIN exome

AF:

0.000657

Gnomad4 NFE exome

AF:

0.00308

Gnomad4 OTH exome

AF:

0.00608

GnomAD4 genome

AF:

0.00362

AC:

551

AN:

152268

Hom.:

Cov.:

AF XY:

0.00379

AC XY:

282

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.00941

Gnomad4 ASJ

AF:

0.0306

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00347

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00560

Hom.:

Bravo

AF:

0.00441

EpiCase

AF:

0.00573

EpiControl

AF:

0.00558

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

PIF1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.18

DANN

Benign

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over