chr19-6744891-C-T

Variant names:

• chr19-6744891-C-T
• rs902157922
• NM_001288962.2:c.881C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001288962.2(TRIP10):​c.881C>T​(p.Ala294Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TRIP10 NM_001288962.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.17
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07359862).
• BP6: Variant 19-6744891-C-T is Benign according to our data. Variant chr19-6744891-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2311743.Status of the report is criteria_provided_single_submitter, 1 stars.

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.881C>T	p.Ala294Val	missense	Exon 9 of 15	NP_001275891.1	Q15642-1
	TRIP10	NM_001288963.3		c.881C>T	p.Ala294Val	missense	Exon 9 of 14	NP_001275892.1	W4VSQ9
	TRIP10	NM_004240.4		c.881C>T	p.Ala294Val	missense	Exon 9 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.881C>T	p.Ala294Val	missense	Exon 9 of 15	ENSP00000320117.7	Q15642-1
	TRIP10	ENST00000596758.5	TSL:1	c.881C>T	p.Ala294Val	missense	Exon 9 of 14	ENSP00000469360.1	W4VSQ9
	TRIP10	ENST00000313285.12	TSL:1	c.881C>T	p.Ala294Val	missense	Exon 9 of 14	ENSP00000320493.6	Q15642-2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461854 Hom.: 0 Cov.: 35 AF XY: 0.00000688 AC XY: 5 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.0000993 AC: 6 AN: 60396

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.12	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.2
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.021
Sift	Benign	0.15	T
Sift4G	Benign	0.090	T
Polyphen		0.0020	B
Vest4		0.078
MutPred		0.23		Loss of glycosylation at S299 (P = 0.2031)
MVP		0.50
MPC		0.18
ClinPred		0.15	T
GERP RS		0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.025
gMVP		0.54
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs902157922; hg19: chr19-6744902;