chr7-100867962-T-C

Variant names:

• chr7-100867962-T-C
• rs577728075
• NM_003302.3:c.211T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003302.3(TRIP6):​c.211T>C​(p.Ser71Pro) 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. 17/22 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. S71A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIP6 NM_003302.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54
• Publications: 0 publications found

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]

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]

ACMG classification

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=0.1033937).

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>C	p.Ser71Pro	missense	Exon 2 of 9	NP_003293.2	Q15654-1
	MIR6875	NR_106935.1		n.-74T>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIP6	ENST00000200457.9	TSL:1 MANE Select	c.211T>C	p.Ser71Pro	missense	Exon 2 of 9	ENSP00000200457.4	Q15654-1
	TRIP6	ENST00000619988.4	TSL:1	c.110-146T>C		intron	N/A	ENSP00000479865.1	Q15654-3
	TRIP6	ENST00000417475.5	TSL:1	n.161T>C		non_coding_transcript_exon	Exon 2 of 6	ENSP00000413817.1	Q15654-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.084
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.55	N
PhyloP100		2.5
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.057
Sift	Benign	0.40	T
Sift4G	Benign	0.34	T
Polyphen		0.19	B
Vest4		0.24
MutPred		0.21		Loss of glycosylation at S71 (P = 0.0481)
MVP		0.30
MPC		0.26
ClinPred		0.51	D
GERP RS		4.3
PromoterAI		0.0025	Neutral
Varity_R		0.19
gMVP		0.25
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs577728075; hg19: chr7-100465584;