4-37960706-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_006607.3(PTTG2):ā€‹c.272A>Gā€‹(p.Lys91Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

PTTG2
NM_006607.3 missense

Scores

3
14

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.349
Variant links:
Genes affected
PTTG2 (HGNC:9691): (pituitary tumor-transforming 2) Predicted to enable SH3 domain binding activity. Predicted to be involved in homologous chromosome segregation and negative regulation of mitotic sister chromatid separation. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
TBC1D1 (HGNC:11578): (TBC1 domain family member 1) TBC1D1 is the founding member of a family of proteins sharing a 180- to 200-amino acid TBC domain presumed to have a role in regulating cell growth and differentiation. These proteins share significant homology with TRE2 (USP6; MIM 604334), yeast Bub2, and CDC16 (MIM 603461) (White et al., 2000 [PubMed 10965142]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16940337).
BP6
Variant 4-37960706-A-G is Benign according to our data. Variant chr4-37960706-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2529202.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PTTG2NM_006607.3 linkuse as main transcriptc.272A>G p.Lys91Arg missense_variant 1/1 ENST00000504686.2
TBC1D1NM_001396959.1 linkuse as main transcriptc.418-53803A>G intron_variant ENST00000698857.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PTTG2ENST00000504686.2 linkuse as main transcriptc.272A>G p.Lys91Arg missense_variant 1/1 NM_006607.3 P1Q9NZH5-2
TBC1D1ENST00000698857.1 linkuse as main transcriptc.418-53803A>G intron_variant NM_001396959.1 A2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250576
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135794
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461892
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsMar 24, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
13
DANN
Uncertain
0.99
Eigen
Benign
-0.55
Eigen_PC
Benign
-0.85
FATHMM_MKL
Benign
0.0032
N
LIST_S2
Benign
0.58
T
M_CAP
Benign
0.0013
T
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-0.88
T
MutationAssessor
Uncertain
2.4
M
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.093
Sift
Uncertain
0.023
D
Sift4G
Benign
0.072
T
Polyphen
1.0
D
Vest4
0.036
MutPred
0.55
Gain of glycosylation at S87 (P = 0.0178);
MVP
0.014
MPC
0.033
ClinPred
0.14
T
GERP RS
0.57
gMVP
0.063

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.

Other links and lift over

dbSNP: rs770131605; hg19: chr4-37962327; API