Genetic Variant PINX1:p.Ala21Ala (chr8-10834732-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_017884.6(PINX1):c.63C>T(p.Ala21Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0522 in 1,613,460 control chromosomes in the GnomAD database, including 2,477 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 0.048 ( 212 hom., cov: 33)

Exomes 𝑓: 0.053 ( 2265 hom. )

Consequence

PINX1
NM_017884.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.52

Publications

10 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP7

Synonymous conserved (PhyloP=-6.52 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PINX1	NM_017884.6 link	c.63C>T	p.Ala21Ala	synonymous_variant	Exon 2 of 7	ENST00000314787.8	NP_060354.4	Q96BK5-1
PINX1	NM_001284356.2 link	c.63C>T	p.Ala21Ala	synonymous_variant	Exon 2 of 6		NP_001271285.1	Q96BK5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PINX1	ENST00000314787.8 link	c.63C>T	p.Ala21Ala	synonymous_variant	Exon 2 of 7	1	NM_017884.6	ENSP00000318966.3		Q96BK5-1
PINX1	ENST00000554914.1 link	c.63C>T	p.Ala21Ala	synonymous_variant	Exon 2 of 6	2		ENSP00000451145.1		A0A0A6YYK5

Frequencies

GnomAD3 genomes

AF:

0.0484

AC:

7356

AN:

152056

Hom.:

212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0408

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.0504

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0776

Gnomad FIN

AF:

0.0341

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0524

Gnomad OTH

AF:

0.0627

GnomAD2 exomes

AF:

0.0495

AC:

12327

AN:

249084

AF XY:

0.0520

show subpopulations

Gnomad AFR exome

AF:

0.0399

Gnomad AMR exome

AF:

0.0385

Gnomad ASJ exome

AF:

0.102

Gnomad EAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.0368

Gnomad NFE exome

AF:

0.0538

Gnomad OTH exome

AF:

0.0685

GnomAD4 exome

AF:

0.0526

AC:

76895

AN:

1461286

Hom.:

2265

Cov.:

AF XY:

0.0534

AC XY:

38795

AN XY:

726958

show subpopulations

African (AFR)

AF:

0.0405

AC:

1354

AN:

33472

American (AMR)

AF:

0.0409

AC:

1827

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.102

AC:

2657

AN:

26126

East Asian (EAS)

AF:

0.000126

AC:

AN:

39690

South Asian (SAS)

AF:

0.0679

AC:

5858

AN:

86230

European-Finnish (FIN)

AF:

0.0374

AC:

1994

AN:

53352

Middle Eastern (MID)

AF:

0.0977

AC:

563

AN:

5764

European-Non Finnish (NFE)

AF:

0.0532

AC:

59164

AN:

1111586

Other (OTH)

AF:

0.0575

AC:

3473

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

3476

6952

10427

13903

17379

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2190

4380

6570

8760

10950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0483

AC:

7356

AN:

152174

Hom.:

212

Cov.:

AF XY:

0.0486

AC XY:

3618

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.0407

AC:

1691

AN:

41520

American (AMR)

AF:

0.0504

AC:

770

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

364

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5182

South Asian (SAS)

AF:

0.0773

AC:

373

AN:

4826

European-Finnish (FIN)

AF:

0.0341

AC:

360

AN:

10568

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0524

AC:

3562

AN:

68002

Other (OTH)

AF:

0.0620

AC:

131

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

365

730

1094

1459

1824

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0487

Hom.:

168

Bravo

AF:

0.0494

Asia WGS

AF:

0.0380

AC:

133

AN:

3478

EpiCase

AF:

0.0600

EpiControl

AF:

0.0616

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.13

(source)

DANN

Benign

0.67

PhyloP100

-6.5

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over