19-6743500-C-T

Variant names:

• chr19-6743500-C-T
• rs144976733
• NM_001288962.2:c.415C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001288962.2(TRIP10):​c.415C>T​(p.Arg139Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R139G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: TRIP10 NM_001288962.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.34
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39269403).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288962.2. 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.415C>T	p.Arg139Cys	missense	Exon 6 of 15	NP_001275891.1	Q15642-1
	TRIP10	NM_001288963.3		c.415C>T	p.Arg139Cys	missense	Exon 6 of 14	NP_001275892.1	W4VSQ9
	TRIP10	NM_004240.4		c.415C>T	p.Arg139Cys	missense	Exon 6 of 14	NP_004231.1	Q15642-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIP10	ENST00000313244.14	TSL:1 MANE Select	c.415C>T	p.Arg139Cys	missense	Exon 6 of 15	ENSP00000320117.7	Q15642-1
	TRIP10	ENST00000596758.5	TSL:1	c.415C>T	p.Arg139Cys	missense	Exon 6 of 14	ENSP00000469360.1	W4VSQ9
	TRIP10	ENST00000313285.12	TSL:1	c.415C>T	p.Arg139Cys	missense	Exon 6 of 14	ENSP00000320493.6	Q15642-2

Frequencies

GnomAD3 genomes AF: 0.0000461 AC: 7 AN: 151766 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000797 AC: 2 AN: 250904 AF XY: 0.00

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461628 Hom.: 0 Cov.: 36 AF XY: 0.00000550 AC XY: 4 AN XY: 727126

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.0000224 AC: 1 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111866

Other (OTH) AF: 0.0000166 AC: 1 AN: 60384

GnomAD4 genome AF: 0.0000461 AC: 7 AN: 151766 Hom.: 0 Cov.: 29 AF XY: 0.0000270 AC XY: 2 AN XY: 74078

African (AFR) AF: 0.000145 AC: 6 AN: 41308

American (AMR) AF: 0.0000660 AC: 1 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000567

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.3
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.47
MutPred		0.37		Loss of MoRF binding (P = 0.0048)
MVP		0.73
MPC		0.82
ClinPred		0.98	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.83
gMVP		0.25
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs144976733; hg19: chr19-6743511;