19-6751282-T-C

Variant names:

• chr19-6751282-T-C
• rs1049232
• ENST00000596758.5:c.1738T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001288963.3(TRIP10):​c.1738T>C​(p.Cys580Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict 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. C580G) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TRIP10 NM_001288963.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.236
• 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]

ENSG00000269680 (HGNC:58603):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2059263).

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>C		3_prime_UTR	Exon 15 of 15	NP_001275891.1	Q15642-1
	TRIP10	NM_001288963.3		c.1738T>C	p.Cys580Arg	missense	Exon 14 of 14	NP_001275892.1	W4VSQ9
	TRIP10	NM_004240.4		c.*71T>C		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>C	p.Cys580Arg	missense	Exon 14 of 14	ENSP00000469360.1	W4VSQ9
	TRIP10	ENST00000313244.14	TSL:1 MANE Select	c.*71T>C		3_prime_UTR	Exon 15 of 15	ENSP00000320117.7	Q15642-1
	TRIP10	ENST00000313285.12	TSL:1	c.*71T>C		3_prime_UTR	Exon 14 of 14	ENSP00000320493.6	Q15642-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457086 Hom.: 0 Cov.: 38 AF XY: 0.00000138 AC XY: 1 AN XY: 724614

African (AFR) AF: 0.00 AC: 0 AN: 33382

American (AMR) AF: 0.00 AC: 0 AN: 44378

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25974

East Asian (EAS) AF: 0.00 AC: 0 AN: 39486

South Asian (SAS) AF: 0.00 AC: 0 AN: 85740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109740

Other (OTH) AF: 0.00 AC: 0 AN: 60210

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Benign	0.64
DEOGEN2	Benign	0.0098	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.98	T
PhyloP100		0.24
Vest4		0.11
MVP		0.33
ClinPred		0.022	T
GERP RS		1.3
Mutation Taster		=99/1	polymorphism

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;