rs1049229

Variant names:

• chr19-6751268-A-G
• rs1049229
• ENST00000596758.5:c.1724A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001288963.3(TRIP10):​c.1724A>G​(p.Glu575Gly) 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 1,611,418 control chromosomes in the GnomAD database, including 29,491 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3800 hom., cov: 32)
  • Exomes 𝑓: 0.18 (25691 hom.)
• Consequence: TRIP10 NM_001288963.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.337

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001078546).
• BP6: Variant 19-6751268-A-G is Benign according to our data. Variant chr19-6751268-A-G is described in ClinVar as [Benign]. Clinvar id is 403567.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.*57A>G		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.*57A>G		3_prime_UTR_variant	Exon 15 of 15	1	NM_001288962.2	ENSP00000320117.7

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33261 AN: 151622 Hom.: 3784 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: 0.275

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.205

GnomAD2 exomes AF: 0.203 AC: 50150 AN: 247002 AF XY: 0.196

Gnomad AFR exome AF: 0.283

Gnomad AMR exome AF: 0.245

Gnomad ASJ exome AF: 0.165

Gnomad EAS exome AF: 0.263

Gnomad FIN exome AF: 0.242

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.208

GnomAD4 exome AF: 0.185 AC: 269860 AN: 1459680 Hom.: 25691 Cov.: 38 AF XY: 0.182 AC XY: 132471 AN XY: 726154

Gnomad4 AFR exome AF: 0.289 AC: 9667 AN: 33432

Gnomad4 AMR exome AF: 0.244 AC: 10881 AN: 44552

Gnomad4 ASJ exome AF: 0.164 AC: 4289 AN: 26088

Gnomad4 EAS exome AF: 0.239 AC: 9465 AN: 39612

Gnomad4 SAS exome AF: 0.137 AC: 11780 AN: 86056

Gnomad4 FIN exome AF: 0.240 AC: 12655 AN: 52662

Gnomad4 NFE exome AF: 0.178 AC: 198074 AN: 1111204

Gnomad4 Remaining exome AF: 0.197 AC: 11903 AN: 60316

GnomAD4 genome AF: 0.220 AC: 33320 AN: 151738 Hom.: 3800 Cov.: 32 AF XY: 0.221 AC XY: 16380 AN XY: 74130

Gnomad4 AFR AF: 0.284 AC: 0.283664 AN: 0.283664

Gnomad4 AMR AF: 0.233 AC: 0.232648 AN: 0.232648

Gnomad4 ASJ AF: 0.152 AC: 0.151873 AN: 0.151873

Gnomad4 EAS AF: 0.275 AC: 0.27459 AN: 0.27459

Gnomad4 SAS AF: 0.135 AC: 0.13536 AN: 0.13536

Gnomad4 FIN AF: 0.249 AC: 0.248573 AN: 0.248573

Gnomad4 NFE AF: 0.181 AC: 0.180873 AN: 0.180873

Gnomad4 OTH AF: 0.210 AC: 0.210227 AN: 0.210227

Alfa AF: 0.197 Hom.: 1706

Bravo AF: 0.225

TwinsUK AF: 0.169 AC: 627

ALSPAC AF: 0.177 AC: 683

ExAC AF: 0.201 AC: 24364

Asia WGS AF: 0.245 AC: 852 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	-0.51	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	12
DANN	Benign	0.89
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0011	T
MetaSVM	Benign	-1.0	T
Vest4		0.11
ClinPred		0.00086	T
GERP RS		1.0
Mutation Taster		=94/6	polymorphism (auto)

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: rs1049229; hg19: chr19-6751279; COSMIC: COSV55585387; COSMIC: COSV55585387;