21-44861255-G-C
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_004339.4(PTTG1IP):c.185C>G(p.Thr62Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00544 in 1,613,530 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0042 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0056 ( 36 hom. )
Consequence
PTTG1IP
NM_004339.4 missense
NM_004339.4 missense
Scores
16
Clinical Significance
Conservation
PhyloP100: 2.66
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.004667282).
BP6
?
Variant 21-44861255-G-C is Benign according to our data. Variant chr21-44861255-G-C is described in ClinVar as [Benign]. Clinvar id is 719550.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAd at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTTG1IP | NM_004339.4 | c.185C>G | p.Thr62Ser | missense_variant | 3/6 | ENST00000330938.8 | |
PTTG1IP | NM_001286822.2 | c.168+4140C>G | intron_variant | ||||
PTTG1IP | NR_104597.2 | n.242+4140C>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTTG1IP | ENST00000330938.8 | c.185C>G | p.Thr62Ser | missense_variant | 3/6 | 1 | NM_004339.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00419 AC: 638AN: 152232Hom.: 3 Cov.: 32
GnomAD3 genomes
?
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638
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32
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GnomAD3 exomes AF: 0.00516 AC: 1294AN: 250938Hom.: 7 AF XY: 0.00498 AC XY: 676AN XY: 135664
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GnomAD4 exome AF: 0.00557 AC: 8136AN: 1461180Hom.: 36 Cov.: 31 AF XY: 0.00535 AC XY: 3890AN XY: 726956
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GnomAD4 genome ? AF: 0.00419 AC: 639AN: 152350Hom.: 3 Cov.: 32 AF XY: 0.00415 AC XY: 309AN XY: 74506
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ESP6500AA
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ExAC
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618
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 02, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T;T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
0.010
.;B;.
Vest4
MutPred
Gain of ubiquitination at K64 (P = 0.0931);Gain of ubiquitination at K64 (P = 0.0931);.;
MVP
MPC
0.25
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at