2-229844482-A-G

Variant names:

• chr2-229844482-A-G
• rs1035833
• NM_001348323.3:c.1028-3555T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001348323.3(TRIP12):​c.1028-3555T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,150 control chromosomes in the GnomAD database, including 5,689 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5689 hom., cov: 32)
• Consequence: TRIP12 NM_001348323.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453
• Publications: 8 publications found

Genes affected

TRIP12 (HGNC:12306): (thyroid hormone receptor interactor 12) The protein encoded by this gene is an E3 ubiquitin-protein ligase involved in the degradation of the p19ARF/ARF isoform of CDKN2A, a tumor suppressor. The encoded protein also plays a role in the DNA damage response by regulating the stability of USP7, which regulates tumor suppressor p53. [provided by RefSeq, Jan 2017]

TRIP12 Gene-Disease associations (from GenCC):

• Clark-Baraitser syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000303081 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIP12	NM_001348323.3	c.1028-3555T>C		intron_variant	Intron 4 of 41	ENST00000675903.1	NP_001335252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIP12	ENST00000675903.1	c.1028-3555T>C		intron_variant	Intron 4 of 41		NM_001348323.3	ENSP00000502713.1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38917 AN: 152032 Hom.: 5690 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.276

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.256 AC: 38916 AN: 152150 Hom.: 5689 Cov.: 32 AF XY: 0.265 AC XY: 19722 AN XY: 74376

African (AFR) AF: 0.119 AC: 4948 AN: 41532

American (AMR) AF: 0.299 AC: 4565 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1148 AN: 3466

East Asian (EAS) AF: 0.398 AC: 2066 AN: 5186

South Asian (SAS) AF: 0.349 AC: 1685 AN: 4828

European-Finnish (FIN) AF: 0.394 AC: 4161 AN: 10552

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19462 AN: 67986

Other (OTH) AF: 0.275 AC: 581 AN: 2110

Alfa AF: 0.287 Hom.: 3628

Bravo AF: 0.245

Asia WGS AF: 0.339 AC: 1175 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.56
DANN	Benign	0.82
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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: rs1035833; hg19: chr2-230709198;