NM_001348323.3:c.1240C>A

Variant names:

• chr2-229836878-G-T
• rs200117340
• NM_001348323.3:c.1240C>A

Variant summary

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

The NM_001348323.3(TRIP12):​c.1240C>A​(p.Arg414Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.000000691 in 1,447,004 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TRIP12 NM_001348323.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.23
• Publications: 0 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

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 (BayesDel_noAF=-0.37).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348323.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIP12	NM_001348323.3	MANE Select	c.1240C>A	p.Arg414Arg	synonymous	Exon 6 of 42	NP_001335252.1
	TRIP12	NM_001348328.1		c.1240C>A	p.Arg414Arg	synonymous	Exon 6 of 42	NP_001335257.1
	TRIP12	NM_001348329.2		c.1240C>A	p.Arg414Arg	synonymous	Exon 6 of 42	NP_001335258.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIP12	ENST00000675903.1	MANE Select	c.1240C>A	p.Arg414Arg	synonymous	Exon 6 of 42	ENSP00000502713.1
	TRIP12	ENST00000389044.8	TSL:1	c.1240C>A	p.Arg414Arg	synonymous	Exon 6 of 42	ENSP00000373696.4
	TRIP12	ENST00000283943.9	TSL:1	c.1114C>A	p.Arg372Arg	synonymous	Exon 5 of 41	ENSP00000283943.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447004 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 720164

African (AFR) AF: 0.00 AC: 0 AN: 32256

American (AMR) AF: 0.00 AC: 0 AN: 40948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25848

East Asian (EAS) AF: 0.00 AC: 0 AN: 37762

South Asian (SAS) AF: 0.00 AC: 0 AN: 84302

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107286

Other (OTH) AF: 0.00 AC: 0 AN: 59750

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	6.8
DANN	Benign	0.70
PhyloP100		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=62/38	polymorphism

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: rs200117340; hg19: chr2-230701594;