TRIP11 p.Asp516Gly

Variant names:

• chr14-92006429-T-C
• rs1018806781
• NM_004239.4:c.1547A>G
• TRIP11 p.Asp516Gly

Your query was ambiguous. Multiple possible variants found:

• chr14-92006429-T-C
• chr14-92006428-AT-GC
• chr14-92006428-AT-TC
• chr14-92006428-AT-CC

Variant summary

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

The NM_004239.4(TRIP11):​c.1547A>G​(p.Asp516Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,612,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TRIP11 NM_004239.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.90
• Publications: 0 publications found

Genes affected

TRIP11 (HGNC:12305): (thyroid hormone receptor interactor 11) This gene was identified based on the interaction of its protein product with thyroid hormone receptor beta. This protein is associated with the Golgi apparatus. The N-terminal region of the protein binds Golgi membranes and the C-terminal region binds the minus ends of microtubules; thus, the protein is thought to play a role in assembly and maintenance of the Golgi ribbon structure around the centrosome. Mutations in this gene cause achondrogenesis type IA.[provided by RefSeq, Mar 2010]

TRIP11 Gene-Disease associations (from GenCC):

• achondrogenesis type IA

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Laboratory for Molecular Medicine, Ambry Genetics
• TRIP11-related skeletal dysplasia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics

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=0.15908277).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004239.4. 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
	TRIP11	NM_004239.4	MANE Select	c.1547A>G	p.Asp516Gly	missense	Exon 11 of 21	NP_004230.2	Q15643-1
	TRIP11	NM_001321851.1		c.1544A>G	p.Asp515Gly	missense	Exon 11 of 21	NP_001308780.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIP11	ENST00000267622.8	TSL:1 MANE Select	c.1547A>G	p.Asp516Gly	missense	Exon 11 of 21	ENSP00000267622.4	Q15643-1
	TRIP11	ENST00000554357.5	TSL:1	c.692A>G	p.Asp231Gly	missense	Exon 5 of 15	ENSP00000451032.1	H0YJ97
	TRIP11	ENST00000913145.1		c.1544A>G	p.Asp515Gly	missense	Exon 11 of 21	ENSP00000583204.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00000401 AC: 1 AN: 249582 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 0.00000137 AC: 2 AN: 1460494 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726608

African (AFR) AF: 0.00 AC: 0 AN: 33452

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39538

South Asian (SAS) AF: 0.00 AC: 0 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5424

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111708

Other (OTH) AF: 0.00 AC: 0 AN: 60302

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74374

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.000131 AC: 2 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Achondrogenesis, type IA (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.067
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.9
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.11
Sift	Benign	0.27	T
Sift4G	Benign	0.24	T
Varity_R		0.11
gMVP		0.21
Mutation Taster		=83/17	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1018806781;

hg19: chr14-92472773;