chr7-100867962-T-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003302.3(TRIP6):c.211T>G(p.Ser71Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000179 in 1,511,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

TRIP6
NM_003302.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.54

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.041385382).

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.211T>G	p.Ser71Ala	missense	Exon 2 of 9	NP_003293.2	Q15654-1
	MIR6875	NR_106935.1		n.-74T>G		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIP6	ENST00000200457.9	TSL:1 MANE Select	c.211T>G	p.Ser71Ala	missense	Exon 2 of 9	ENSP00000200457.4	Q15654-1
TRIP6	ENST00000619988.4	TSL:1	c.110-146T>G		intron	N/A	ENSP00000479865.1	Q15654-3
TRIP6	ENST00000417475.5	TSL:1	n.161T>G		non_coding_transcript_exon	Exon 2 of 6	ENSP00000413817.1	Q15654-2

Frequencies

GnomAD3 genomes

AF:

0.0000793

AC:

AN:

151368

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000329

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000590

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000855

AC:

AN:

163774

AF XY:

0.000114

show subpopulations

Gnomad AFR exome

AF:

0.0000737

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000118

Gnomad NFE exome

AF:

0.000139

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000190

AC:

258

AN:

1359658

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

126

AN XY:

666946

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29500

American (AMR)

AF:

0.00

AC:

AN:

27508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19688

East Asian (EAS)

AF:

0.00

AC:

AN:

37348

South Asian (SAS)

AF:

0.00

AC:

AN:

69538

European-Finnish (FIN)

AF:

0.000222

AC:

AN:

49472

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5264

European-Non Finnish (NFE)

AF:

0.000225

AC:

240

AN:

1065572

Other (OTH)

AF:

0.000126

AC:

AN:

55768

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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

AF:

0.0000792

AC:

AN:

151486

Hom.:

Cov.:

AF XY:

0.0000946

AC XY:

AN XY:

74004

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41264

American (AMR)

AF:

0.000328

AC:

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5102

South Asian (SAS)

AF:

0.00

AC:

AN:

4780

European-Finnish (FIN)

AF:

0.000190

AC:

AN:

10530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000590

AC:

AN:

67810

Other (OTH)

AF:

0.00

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000329

Hom.:

ExAC

AF:

0.0000503

AC:

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

0.069

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.019

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.51

M_CAP

Benign

0.016

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

2.5

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.40

REVEL

Benign

0.090

Sift

Benign

0.42

Sift4G

Benign

0.89

Polyphen

0.0030

Vest4

0.12

MVP

0.33

MPC

0.17

ClinPred

0.098

GERP RS

4.3

PromoterAI

0.020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.18

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over