19-6751282-T-G

Variant names:

• chr19-6751282-T-G
• rs1049232
• ENST00000596758.5:c.1738T>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.1738T>G​(p.Cys580Gly) 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 1,608,724 control chromosomes in the GnomAD database, including 29,568 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 (3871 hom., cov: 32)
  • Exomes 𝑓: 0.19 (25697 hom.)
• Consequence: TRIP10 NM_001288963.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.236
• Publications: 36 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=0.0013584793).
• BP6: Variant 19-6751282-T-G is Benign according to our data. Variant chr19-6751282-T-G is described in ClinVar as Benign. ClinVar VariationId is 403569.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288963.3. 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
	TRIP10	NM_001288962.2	MANE Select	c.*71T>G		3_prime_UTR	Exon 15 of 15	NP_001275891.1	Q15642-1
	TRIP10	NM_001288963.3		c.1738T>G	p.Cys580Gly	missense	Exon 14 of 14	NP_001275892.1	W4VSQ9
	TRIP10	NM_004240.4		c.*71T>G		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.1738T>G	p.Cys580Gly	missense	Exon 14 of 14	ENSP00000469360.1	W4VSQ9
	TRIP10	ENST00000313244.14	TSL:1 MANE Select	c.*71T>G		3_prime_UTR	Exon 15 of 15	ENSP00000320117.7	Q15642-1
	TRIP10	ENST00000313285.12	TSL:1	c.*71T>G		3_prime_UTR	Exon 14 of 14	ENSP00000320493.6	Q15642-2

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33426 AN: 151888 Hom.: 3855 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.207

GnomAD2 exomes AF: 0.204 AC: 49716 AN: 243922 AF XY: 0.197

Gnomad AFR exome AF: 0.285

Gnomad AMR exome AF: 0.247

Gnomad ASJ exome AF: 0.165

Gnomad EAS exome AF: 0.264

Gnomad FIN exome AF: 0.242

Gnomad NFE exome AF: 0.184

Gnomad OTH exome AF: 0.208

GnomAD4 exome AF: 0.185 AC: 269531 AN: 1456718 Hom.: 25697 Cov.: 38 AF XY: 0.183 AC XY: 132269 AN XY: 724440

African (AFR) AF: 0.290 AC: 9665 AN: 33364

American (AMR) AF: 0.245 AC: 10872 AN: 44346

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 4270 AN: 25964

East Asian (EAS) AF: 0.239 AC: 9447 AN: 39468

South Asian (SAS) AF: 0.135 AC: 11607 AN: 85722

European-Finnish (FIN) AF: 0.240 AC: 12585 AN: 52412

Middle Eastern (MID) AF: 0.201 AC: 1158 AN: 5754

European-Non Finnish (NFE) AF: 0.178 AC: 198020 AN: 1109496

Other (OTH) AF: 0.198 AC: 11907 AN: 60192

GnomAD4 genome AF: 0.220 AC: 33485 AN: 152006 Hom.: 3871 Cov.: 32 AF XY: 0.222 AC XY: 16467 AN XY: 74314

African (AFR) AF: 0.285 AC: 11790 AN: 41404

American (AMR) AF: 0.235 AC: 3590 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 527 AN: 3470

East Asian (EAS) AF: 0.275 AC: 1417 AN: 5162

South Asian (SAS) AF: 0.133 AC: 642 AN: 4822

European-Finnish (FIN) AF: 0.250 AC: 2640 AN: 10574

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.181 AC: 12310 AN: 67976

Other (OTH) AF: 0.212 AC: 448 AN: 2112

Alfa AF: 0.197 Hom.: 7572

Bravo AF: 0.225

TwinsUK AF: 0.170 AC: 629

ALSPAC AF: 0.177 AC: 683

ExAC AF: 0.201 AC: 24325

Asia WGS AF: 0.245 AC: 852 AN: 3478

EpiCase AF: 0.176

EpiControl AF: 0.188

ClinVar

ClinVar submissions

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	0.057
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	12
DANN	Benign	0.62
DEOGEN2	Benign	0.0098	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.24
Vest4		0.25
ClinPred		0.00091	T
GERP RS		1.3
Mutation Taster		=99/1	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: rs1049232; hg19: chr19-6751293; COSMIC: COSV55585395; COSMIC: COSV55585395;