12-106321690-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152772.3(TCP11L2):​c.619A>T​(p.Ile207Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

TCP11L2
NM_152772.3 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74
Variant links:
Genes affected
TCP11L2 (HGNC:28627): (t-complex 11 like 2) Predicted to be involved in signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21204758).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TCP11L2NM_152772.3 linkc.619A>T p.Ile207Phe missense_variant Exon 5 of 10 ENST00000299045.8 NP_689985.1 Q8N4U5-1A0A024RBH4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TCP11L2ENST00000299045.8 linkc.619A>T p.Ile207Phe missense_variant Exon 5 of 10 1 NM_152772.3 ENSP00000299045.3 Q8N4U5-1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152218
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000994
AC:
25
AN:
251422
Hom.:
0
AF XY:
0.000132
AC XY:
18
AN XY:
135896
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
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:
0.000193
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000224
AC:
328
AN:
1461822
Hom.:
0
Cov.:
31
AF XY:
0.000206
AC XY:
150
AN XY:
727218
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000272
Gnomad4 OTH exome
AF:
0.000265
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152218
Hom.:
0
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000135
Hom.:
0
Bravo
AF:
0.000110
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000576
AC:
7
EpiCase
AF:
0.000436
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.619A>T (p.I207F) alteration is located in exon 5 (coding exon 4) of the TCP11L2 gene. This alteration results from a A to T substitution at nucleotide position 619, causing the isoleucine (I) at amino acid position 207 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.023
.;T;.;.
Eigen
Benign
0.18
Eigen_PC
Benign
0.19
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.90
D;D;D;D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.21
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
2.9
M;M;.;.
PrimateAI
Benign
0.39
T
PROVEAN
Uncertain
-3.0
D;N;D;D
REVEL
Benign
0.18
Sift
Benign
0.039
D;D;D;D
Sift4G
Uncertain
0.032
D;D;D;D
Polyphen
0.75, 0.74
.;P;P;.
Vest4
0.80
MVP
0.34
MPC
0.30
ClinPred
0.55
D
GERP RS
2.5
Varity_R
0.18
gMVP
0.65

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: rs138672494; hg19: chr12-106715468; API