rs2075756

Variant names:

• chr7-100868819-G-A
• rs2075756
• NM_003302.3:c.688G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-100868819-G-A
• chr7-100868819-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003302.3(TRIP6):​c.688G>A​(p.Val230Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,521,606 control chromosomes in the GnomAD database, including 63,192 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.25 (5631 hom., cov: 32)
  • Exomes 𝑓: 0.28 (57561 hom.)
• Consequence: TRIP6 NM_003302.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011588335).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIP6	NM_003302.3	c.688G>A	p.Val230Ile	missense_variant	Exon 4 of 9	ENST00000200457.9	NP_003293.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIP6	ENST00000200457.9	c.688G>A	p.Val230Ile	missense_variant	Exon 4 of 9	1	NM_003302.3	ENSP00000200457.4

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38008 AN: 152008 Hom.: 5620 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.276

GnomAD3 exomes AF: 0.299 AC: 50866 AN: 169870 Hom.: 8530 AF XY: 0.295 AC XY: 27022 AN XY: 91556

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.486

Gnomad ASJ exome AF: 0.236

Gnomad EAS exome AF: 0.448

Gnomad SAS exome AF: 0.265

Gnomad FIN exome AF: 0.268

Gnomad NFE exome AF: 0.275

Gnomad OTH exome AF: 0.296

GnomAD4 exome AF: 0.284 AC: 388630 AN: 1369480 Hom.: 57561 Cov.: 35 AF XY: 0.283 AC XY: 190337 AN XY: 673166

Gnomad4 AFR exome AF: 0.0972

Gnomad4 AMR exome AF: 0.477

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.450

Gnomad4 SAS exome AF: 0.268

Gnomad4 FIN exome AF: 0.266

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.283

GnomAD4 genome AF: 0.250 AC: 38018 AN: 152126 Hom.: 5631 Cov.: 32 AF XY: 0.256 AC XY: 19045 AN XY: 74368

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.277

Alfa AF: 0.270 Hom.: 10447

Bravo AF: 0.260

ESP6500AA AF: 0.112 AC: 414

ESP6500EA AF: 0.269 AC: 2193

ExAC AF: 0.285 AC: 33949

Asia WGS AF: 0.317 AC: 1102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.13
Sift	Benign	0.40	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.016
MPC		0.17
ClinPred		0.015	T
GERP RS		5.1
Varity_R		0.071
gMVP		0.20

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

Other links and lift over

dbSNP: rs2075756; hg19: chr7-100466441; COSMIC: COSV51931062; COSMIC: COSV51931062;