2-229768856-T-TAAATC

Position:

• chr2-229768856-T-TAAATC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001348323.3(TRIP12):​c.5904-138_5904-137insGATTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 802,774 control chromosomes in the GnomAD database, including 42,755 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (8145 hom., cov: 0)
  • Exomes 𝑓: 0.31 (34610 hom.)
• Consequence: TRIP12 NM_001348323.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.827

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-229768856-T-TAAATC is Benign according to our data. Variant chr2-229768856-T-TAAATC is described in ClinVar as [Benign]. Clinvar id is 1244075.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIP12	NM_001348323.3	c.5904-138_5904-137insGATTT		intron_variant		ENST00000675903.1	NP_001335252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIP12	ENST00000675903.1	c.5904-138_5904-137insGATTT		intron_variant			NM_001348323.3	ENSP00000502713.1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49403 AN: 151840 Hom.: 8140 Cov.: 0

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.423

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.332

GnomAD4 exome AF: 0.313 AC: 203980 AN: 650816 Hom.: 34610 AF XY: 0.315 AC XY: 105213 AN XY: 334336

Gnomad4 AFR exome AF: 0.299

Gnomad4 AMR exome AF: 0.253

Gnomad4 ASJ exome AF: 0.410

Gnomad4 EAS exome AF: 0.234

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.318

Gnomad4 NFE exome AF: 0.319

Gnomad4 OTH exome AF: 0.325

GnomAD4 genome AF: 0.325 AC: 49435 AN: 151958 Hom.: 8145 Cov.: 0 AF XY: 0.322 AC XY: 23957 AN XY: 74310

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.329

Alfa AF: 0.334 Hom.: 935

Bravo AF: 0.319

Asia WGS AF: 0.256 AC: 893 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 17, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3215750; hg19: chr2-230633572;