rs748045368

Variant summary

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

The NM_003302.3(TRIP6):​c.563C>A​(p.Ala188Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000555 in 1,441,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A188V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

TRIP6
NM_003302.3 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41
Variant links:
Genes affected
TRIP6 (HGNC:12311): (thyroid hormone receptor interactor 6) This gene is a member of the zyxin family and encodes a protein with three LIM zinc-binding domains. This protein localizes to focal adhesion sites and along actin stress fibers. Recruitment of this protein to the plasma membrane occurs in a lysophosphatidic acid (LPA)-dependent manner and it regulates LPA-induced cell migration. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

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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=0.11310962).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIP6NM_003302.3 linkc.563C>A p.Ala188Asp missense_variant Exon 4 of 9 ENST00000200457.9 NP_003293.2 Q15654-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIP6ENST00000200457.9 linkc.563C>A p.Ala188Asp missense_variant Exon 4 of 9 1 NM_003302.3 ENSP00000200457.4 Q15654-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000901
AC:
2
AN:
221898
Hom.:
0
AF XY:
0.00000814
AC XY:
1
AN XY:
122846
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000319
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:
0.0000102
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000555
AC:
8
AN:
1441170
Hom.:
0
Cov.:
32
AF XY:
0.00000699
AC XY:
5
AN XY:
715234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000239
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:
0.00000635
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000835
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
18
DANN
Benign
0.96
DEOGEN2
Benign
0.034
T
Eigen
Benign
-0.38
Eigen_PC
Benign
-0.30
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.62
T
M_CAP
Benign
0.067
D
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.81
L
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.039
Sift
Benign
0.41
T
Sift4G
Benign
0.55
T
Polyphen
0.44
B
Vest4
0.30
MutPred
0.25
Gain of relative solvent accessibility (P = 0.0249);
MVP
0.24
MPC
0.46
ClinPred
0.077
T
GERP RS
1.8
Varity_R
0.099
gMVP
0.44

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs748045368; hg19: chr7-100466316; API