7-100867559-G-A

Variant names:

• chr7-100867559-G-A
• NM_003302.3:c.62G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003302.3(TRIP6):​c.62G>A​(p.Arg21Lys) 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. 15/21 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)
• Consequence: TRIP6 NM_003302.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.47

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 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=0.09674096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIP6	NM_003302.3	c.62G>A	p.Arg21Lys	missense_variant	Exon 1 of 9	ENST00000200457.9	NP_003293.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIP6	ENST00000200457.9	c.62G>A	p.Arg21Lys	missense_variant	Exon 1 of 9	1	NM_003302.3	ENSP00000200457.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.62G>A (p.R21K) alteration is located in exon 1 (coding exon 1) of the TRIP6 gene. This alteration results from a G to A substitution at nucleotide position 62, causing the arginine (R) at amino acid position 21 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.019	T;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.097	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.15	N;.
REVEL	Benign	0.065
Sift	Benign	0.12	T;.
Sift4G	Benign	0.73	T;T
Polyphen		0.0	B;.
Vest4		0.086
MutPred		0.16		Gain of ubiquitination at R21 (P = 0.0094);Gain of ubiquitination at R21 (P = 0.0094);
MVP		0.38
MPC		0.21
ClinPred		0.096	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.077
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-100465181;