19-6743567-A-G

Variant names:

• chr19-6743567-A-G
• rs1287022392
• NM_001288962.2:c.482A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001288962.2(TRIP10):​c.482A>G​(p.Asp161Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,422,554 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TRIP10 NM_001288962.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.26

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIP10	NM_001288962.2	c.482A>G	p.Asp161Gly	missense_variant	Exon 6 of 15	ENST00000313244.14	NP_001275891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIP10	ENST00000313244.14	c.482A>G	p.Asp161Gly	missense_variant	Exon 6 of 15	1	NM_001288962.2	ENSP00000320117.7

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1422554 Hom.: 0 Cov.: 36 AF XY: 0.00000141 AC XY: 1 AN XY: 707296

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000276

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 07, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.482A>G (p.D161G) alteration is located in exon 6 (coding exon 6) of the TRIP10 gene. This alteration results from a A to G substitution at nucleotide position 482, causing the aspartic acid (D) at amino acid position 161 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T;.;D;T;.
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	1.0	D;D;D;D;D
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.63	D;D;D;D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.6	.;L;L;.;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-6.2	.;D;D;.;.
REVEL	Benign	0.27
Sift	Uncertain	0.0010	.;D;D;.;.
Sift4G	Uncertain	0.0020	D;D;D;D;D
Polyphen		0.0020	.;B;B;.;.
Vest4		0.54
MutPred		0.31		.;Gain of MoRF binding (P = 0.0312);Gain of MoRF binding (P = 0.0312);Gain of MoRF binding (P = 0.0312);.;
MVP		0.76
MPC		0.24
ClinPred		0.99	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.93
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1287022392; hg19: chr19-6743578;