ENST00000596758.5:c.1726C>T

Variant names:

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

Variant summary

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

The ENST00000596758.5(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. 11/14 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 ENST00000596758.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.70
• Publications: 32 publications found

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:58603):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000596758.5. 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
	TRIP10	NM_001288962.2	MANE Select	c.*59C>T		3_prime_UTR	Exon 15 of 15	NP_001275891.1	Q15642-1
	TRIP10	NM_001288963.3		c.1726C>T	p.Pro576Ser	missense	Exon 14 of 14	NP_001275892.1	W4VSQ9
	TRIP10	NM_004240.4		c.*59C>T		3_prime_UTR	Exon 14 of 14	NP_004231.1	Q15642-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIP10	ENST00000596758.5	TSL:1	c.1726C>T	p.Pro576Ser	missense	Exon 14 of 14	ENSP00000469360.1	W4VSQ9
	TRIP10	ENST00000313244.14	TSL:1 MANE Select	c.*59C>T		3_prime_UTR	Exon 15 of 15	ENSP00000320117.7	Q15642-1
	TRIP10	ENST00000313285.12	TSL:1	c.*59C>T		3_prime_UTR	Exon 14 of 14	ENSP00000320493.6	Q15642-2

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

GnomAD2 exomes AF: 0.203 AC: 50086 AN: 246766 AF XY: 0.196

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 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

African (AFR) AF: 0.289 AC: 9669 AN: 33434

American (AMR) AF: 0.244 AC: 10881 AN: 44530

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 4289 AN: 26058

East Asian (EAS) AF: 0.239 AC: 9470 AN: 39590

South Asian (SAS) AF: 0.135 AC: 11600 AN: 86000

European-Finnish (FIN) AF: 0.240 AC: 12642 AN: 52642

Middle Eastern (MID) AF: 0.199 AC: 1145 AN: 5754

European-Non Finnish (NFE) AF: 0.178 AC: 198070 AN: 1110942

Other (OTH) AF: 0.197 AC: 11895 AN: 60288

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

African (AFR) AF: 0.283 AC: 11715 AN: 41346

American (AMR) AF: 0.232 AC: 3550 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 527 AN: 3472

East Asian (EAS) AF: 0.274 AC: 1406 AN: 5140

South Asian (SAS) AF: 0.133 AC: 640 AN: 4810

European-Finnish (FIN) AF: 0.248 AC: 2612 AN: 10530

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.181 AC: 12285 AN: 67950

Other (OTH) AF: 0.210 AC: 444 AN: 2114

Alfa AF: 0.195 Hom.: 1731

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
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
PhyloP100		1.7
Vest4		0.37
ClinPred		0.00044	T
GERP RS		-0.062
Mutation Taster		=98/2	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

Other links and lift over

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