Genetic Variant NM_003302.3:c.563C>A (chr7-100868694-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/22 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

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41

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:

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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=0.11310962).

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.563C>A	p.Ala188Asp	missense	Exon 4 of 9	NP_003293.2	Q15654-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRIP6	ENST00000200457.9	TSL:1 MANE Select	c.563C>A	p.Ala188Asp	missense	Exon 4 of 9	ENSP00000200457.4	Q15654-1
TRIP6	ENST00000619988.4	TSL:1	c.*192C>A		3_prime_UTR	Exon 3 of 8	ENSP00000479865.1	Q15654-3
TRIP6	ENST00000417475.5	TSL:1	n.*192C>A		non_coding_transcript_exon	Exon 4 of 6	ENSP00000413817.1	Q15654-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000901

AC:

AN:

221898

AF XY:

0.00000814

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000102

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000555

AC:

AN:

1441170

Hom.:

Cov.:

AF XY:

0.00000699

AC XY:

AN XY:

715234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32740

American (AMR)

AF:

0.0000239

AC:

AN:

41888

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25100

East Asian (EAS)

AF:

0.00

AC:

AN:

39374

South Asian (SAS)

AF:

0.00

AC:

AN:

84492

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51364

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5152

European-Non Finnish (NFE)

AF:

0.00000635

AC:

AN:

1101822

Other (OTH)

AF:

0.00

AC:

AN:

59238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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.:

ExAC

AF:

0.00000835

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.034

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.62

M_CAP

Benign

0.067

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.81

PhyloP100

1.4

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.1

REVEL

Benign

0.039

Sift

Benign

0.41

Sift4G

Benign

0.55

Polyphen

0.44

Vest4

0.30

MutPred

0.25

Gain of relative solvent accessibility (P = 0.0249)

MVP

0.24

MPC

0.46

ClinPred

0.077

GERP RS

1.8

PromoterAI

-0.040

Neutral

(source)

Varity_R

0.099

gMVP

0.44

Mutation Taster

=81/19

polymorphism

(source)

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

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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