19-6751270-C-T

Variant names:

• chr19-6751270-C-T
• rs1049230
• ENST00000596758.5:c.1726C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001288963.3(TRIP10):​c.1726C>T​(p.Pro576Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,611,074 control chromosomes in the GnomAD database, including 29,470 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3795 hom., cov: 32)
  • Exomes 𝑓: 0.18 (25675 hom.)
• Consequence: TRIP10 NM_001288963.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.70

Genes affected

TRIP10 (HGNC:12304): (thyroid hormone receptor interactor 10) Enables identical protein binding activity. Predicted to be involved in actin cytoskeleton organization; endocytosis; and signal transduction. Located in nucleoplasm. Biomarker of Huntington's disease. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000269680 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015844703).
• BP6: Variant 19-6751270-C-T is Benign according to our data. Variant chr19-6751270-C-T is described in ClinVar as [Benign]. Clinvar id is 403568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIP10	NM_001288962.2	c.*59C>T		3_prime_UTR_variant	Exon 15 of 15	ENST00000313244.14	NP_001275891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIP10	ENST00000313244.14	c.*59C>T		3_prime_UTR_variant	Exon 15 of 15	1	NM_001288962.2	ENSP00000320117.7

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33240 AN: 151718 Hom.: 3779 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.205

GnomAD3 exomes AF: 0.203 AC: 50086 AN: 246766 Hom.: 5427 AF XY: 0.196 AC XY: 26290 AN XY: 134250

Gnomad AFR exome AF: 0.283

Gnomad AMR exome AF: 0.246

Gnomad ASJ exome AF: 0.165

Gnomad EAS exome AF: 0.263

Gnomad SAS exome AF: 0.134

Gnomad FIN exome AF: 0.242

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.207

GnomAD4 exome AF: 0.185 AC: 269661 AN: 1459238 Hom.: 25675 Cov.: 38 AF XY: 0.182 AC XY: 132321 AN XY: 725900

Gnomad4 AFR exome AF: 0.289

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.239

Gnomad4 SAS exome AF: 0.135

Gnomad4 FIN exome AF: 0.240

Gnomad4 NFE exome AF: 0.178

Gnomad4 OTH exome AF: 0.197

GnomAD4 genome AF: 0.219 AC: 33299 AN: 151836 Hom.: 3795 Cov.: 32 AF XY: 0.221 AC XY: 16368 AN XY: 74200

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.210

Alfa AF: 0.193 Hom.: 1568

Bravo AF: 0.225

TwinsUK AF: 0.169 AC: 627

ALSPAC AF: 0.177 AC: 682

ExAC AF: 0.201 AC: 24326

Asia WGS AF: 0.245 AC: 850 AN: 3478

EpiCase AF: 0.176

EpiControl AF: 0.187

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	14
DANN	Benign	0.77
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.37	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.98	T
Vest4		0.37
ClinPred		0.00044	T
GERP RS		-0.062

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

LitVar

Other links and lift over

dbSNP: rs1049230; hg19: chr19-6751281; COSMIC: COSV55585313; COSMIC: COSV55585313;