Genetic Variant PTTG1IP:c.115+679A>G (chr21-44872823-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004339.4(PTTG1IP):c.115+679A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 152,320 control chromosomes in the GnomAD database, including 34,767 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 0.67 ( 34756 hom., cov: 35)

Exomes 𝑓: 0.59 ( 11 hom. )

Consequence

PTTG1IP
NM_004339.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.912

Publications

4 publications found

Variant links:

Genes affected

PTTG1IP (HGNC:13524): (PTTG1 interacting protein) This gene encodes a single-pass type I integral membrane protein, which binds to pituitary tumor-transforming 1 protein (PTTG1), and facilitates translocation of PTTG1 into the nucleus. Coexpression of this protein and PTTG1 induces transcriptional activation of basic fibroblast growth factor. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2013]

PTTG1IP links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004339.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PTTG1IP	NM_004339.4	MANE Select	c.115+679A>G	intron	N/A	NP_004330.1	P53801
PTTG1IP	NM_001286822.2		c.115+679A>G	intron	N/A	NP_001273751.1	B4DPZ0
PTTG1IP	NR_104597.2		n.189+679A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PTTG1IP	ENST00000330938.8	TSL:1 MANE Select	c.115+679A>G	intron	N/A	ENSP00000328325.3	P53801
PTTG1IP	ENST00000898882.1		c.115+679A>G	intron	N/A	ENSP00000568941.1
PTTG1IP	ENST00000898881.1		c.115+679A>G	intron	N/A	ENSP00000568940.1

Frequencies

GnomAD3 genomes

AF:

0.671

AC:

102038

AN:

152132

Hom.:

34692

Cov.:

show subpopulations

Gnomad AFR

AF:

0.784

Gnomad AMI

AF:

0.502

Gnomad AMR

AF:

0.623

Gnomad ASJ

AF:

0.627

Gnomad EAS

AF:

0.764

Gnomad SAS

AF:

0.688

Gnomad FIN

AF:

0.621

Gnomad MID

AF:

0.671

Gnomad NFE

AF:

0.616

Gnomad OTH

AF:

0.683

GnomAD4 exome

AF:

0.586

AC:

AN:

Hom.:

Cov.:

AF XY:

0.648

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.569

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.671

AC:

102166

AN:

152250

Hom.:

34756

Cov.:

AF XY:

0.670

AC XY:

49897

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.785

AC:

32623

AN:

41562

American (AMR)

AF:

0.623

AC:

9525

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.627

AC:

2176

AN:

3472

East Asian (EAS)

AF:

0.764

AC:

3951

AN:

5174

South Asian (SAS)

AF:

0.689

AC:

3330

AN:

4834

European-Finnish (FIN)

AF:

0.621

AC:

6583

AN:

10602

Middle Eastern (MID)

AF:

0.694

AC:

204

AN:

294

European-Non Finnish (NFE)

AF:

0.616

AC:

41864

AN:

67996

Other (OTH)

AF:

0.687

AC:

1453

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1786

3572

5357

7143

8929

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

808

1616

2424

3232

4040

<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:

0.511

Hom.:

1436

Bravo

AF:

0.678

Asia WGS

AF:

0.724

AC:

2518

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

2.4

(source)

DANN

Benign

0.21

PhyloP100

-0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over