rs145607668

Variant names:

• chr7-100868220-G-A
• rs145607668
• NM_003302.3:c.350G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-100868220-G-A
• chr7-100868220-G-C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_003302.3(TRIP6):​c.350G>A​(p.Arg117Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000682 in 1,608,126 control chromosomes in the GnomAD database, including 9 homozygotes. 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (5 hom.)
• Consequence: TRIP6 NM_003302.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.41
• Publications: 1 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004185885).
• BP6: Variant 7-100868220-G-A is Benign according to our data. Variant chr7-100868220-G-A is described in ClinVar as Benign. ClinVar VariationId is 781044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4 gene

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.350G>A	p.Arg117Gln	missense	Exon 3 of 9	NP_003293.2	Q15654-1
	MIR6875	NR_106935.1		n.*113G>A		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIP6	ENST00000200457.9	TSL:1 MANE Select	c.350G>A	p.Arg117Gln	missense	Exon 3 of 9	ENSP00000200457.4	Q15654-1
	TRIP6	ENST00000619988.4	TSL:1	c.222G>A	p.Ala74Ala	synonymous	Exon 2 of 8	ENSP00000479865.1	Q15654-3
	TRIP6	ENST00000417475.5	TSL:1	n.300G>A		non_coding_transcript_exon	Exon 3 of 6	ENSP00000413817.1	Q15654-2

Frequencies

GnomAD3 genomes AF: 0.00347 AC: 528 AN: 152078 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00108 AC: 265 AN: 246490 AF XY: 0.000725

Gnomad AFR exome AF: 0.0129

Gnomad AMR exome AF: 0.00151

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000359

Gnomad OTH exome AF: 0.000668

GnomAD4 exome AF: 0.000389 AC: 566 AN: 1455930 Hom.: 5 Cov.: 32 AF XY: 0.000300 AC XY: 217 AN XY: 723714

African (AFR) AF: 0.0127 AC: 421 AN: 33250

American (AMR) AF: 0.00157 AC: 69 AN: 44022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25964

East Asian (EAS) AF: 0.00 AC: 0 AN: 39520

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52660

Middle Eastern (MID) AF: 0.000557 AC: 3 AN: 5388

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1109040

Other (OTH) AF: 0.000966 AC: 58 AN: 60040

GnomAD4 genome AF: 0.00349 AC: 531 AN: 152196 Hom.: 4 Cov.: 32 AF XY: 0.00340 AC XY: 253 AN XY: 74406

African (AFR) AF: 0.0123 AC: 509 AN: 41500

American (AMR) AF: 0.00111 AC: 17 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68010

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00147 Hom.: 2

Bravo AF: 0.00386

ESP6500AA AF: 0.0125 AC: 55

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00119 AC: 145

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000594

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.099	N
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.4
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.089
Sift	Benign	0.085	T
Sift4G	Benign	0.67	T
Polyphen		0.70	P
Vest4		0.24
MVP		0.42
MPC		0.24
ClinPred		0.0057	T
GERP RS		3.3
Varity_R		0.056
gMVP		0.29
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs145607668; hg19: chr7-100465842; COSMIC: COSV107215812; COSMIC: COSV107215812;