rs577728075

Variant summary

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

The NM_003302.3(TRIP6):​c.211T>C​(p.Ser71Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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. S71A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

TRIP6
NM_003302.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.54
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]
MIR6875 (HGNC:50015): (microRNA 6875) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

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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=0.1033937).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIP6NM_003302.3 linkc.211T>C p.Ser71Pro missense_variant Exon 2 of 9 ENST00000200457.9 NP_003293.2 Q15654-1
MIR6875NR_106935.1 linkn.-74T>C upstream_gene_variant
MIR6875unassigned_transcript_1288 n.-79T>C upstream_gene_variant
MIR6875unassigned_transcript_1289 n.-118T>C upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIP6ENST00000200457.9 linkc.211T>C p.Ser71Pro missense_variant Exon 2 of 9 1 NM_003302.3 ENSP00000200457.4 Q15654-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.063
BayesDel_addAF
Benign
-0.090
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
19
DANN
Benign
0.94
DEOGEN2
Benign
0.016
T
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.084
FATHMM_MKL
Benign
0.57
D
LIST_S2
Benign
0.65
T
M_CAP
Benign
0.040
D
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
0.55
N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.12
N
REVEL
Benign
0.057
Sift
Benign
0.40
T
Sift4G
Benign
0.34
T
Polyphen
0.19
B
Vest4
0.24
MutPred
0.21
Loss of glycosylation at S71 (P = 0.0481);
MVP
0.30
MPC
0.26
ClinPred
0.51
D
GERP RS
4.3
Varity_R
0.19
gMVP
0.25

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: rs577728075; hg19: chr7-100465584; API