NM_003302.3:c.191G>A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003302.3(TRIP6):c.191G>A(p.Arg64Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000022 in 1,362,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

TRIP6
NM_003302.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.847

Publications

0 publications found

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]

TRIP6 links:

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]

MIR6875 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07687217).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003302.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIP6	NM_003302.3	MANE Select	c.191G>A	p.Arg64Gln	missense	Exon 2 of 9	NP_003293.2	Q15654-1
	MIR6875	NR_106935.1		n.-94G>A		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIP6	ENST00000200457.9	TSL:1 MANE Select	c.191G>A	p.Arg64Gln	missense	Exon 2 of 9	ENSP00000200457.4	Q15654-1
TRIP6	ENST00000619988.4	TSL:1	c.110-166G>A		intron	N/A	ENSP00000479865.1	Q15654-3
TRIP6	ENST00000417475.5	TSL:1	n.141G>A		non_coding_transcript_exon	Exon 2 of 6	ENSP00000413817.1	Q15654-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000366

AC:

AN:

163990

AF XY:

0.0000456

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000503

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000220

AC:

AN:

1362074

Hom.:

Cov.:

AF XY:

0.0000254

AC XY:

AN XY:

668626

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29614

American (AMR)

AF:

0.000109

AC:

AN:

27452

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19672

East Asian (EAS)

AF:

0.00

AC:

AN:

37502

South Asian (SAS)

AF:

0.0000144

AC:

AN:

69592

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49484

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5296

European-Non Finnish (NFE)

AF:

0.0000244

AC:

AN:

1067552

Other (OTH)

AF:

0.00

AC:

AN:

55910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000504

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.016

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.73

M_CAP

Benign

0.030

MetaRNN

Benign

0.077

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.90

PhyloP100

0.85

PrimateAI

Benign

0.45

PROVEAN

Benign

0.050

REVEL

Benign

0.058

Sift

Benign

0.33

Sift4G

Benign

0.66

Polyphen

0.30

Vest4

0.22

MutPred

0.22

Gain of glycosylation at P66 (P = 0.1484)

MVP

0.39

MPC

0.24

ClinPred

0.15

GERP RS

4.3

PromoterAI

-0.0074

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.054

gMVP

0.30

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over