5-896542-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004237.4(TRIP13):c.259-123G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,045,102 control chromosomes in the GnomAD database, including 898 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.047 (525 hom., cov: 32)
  • Exomes 𝑓: 0.0070 (373 hom.)
• Consequence: TRIP13 NM_004237.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0450

Genes affected

TRIP13 (HGNC:12307): (thyroid hormone receptor interactor 13) This gene encodes a protein that interacts with thyroid hormone receptors, also known as hormone-dependent transcription factors. The gene product interacts specifically with the ligand binding domain. This gene is one of several that may play a role in early-stage non-small cell lung cancer. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-896542-G-T is Benign according to our data. Variant chr5-896542-G-T is described in ClinVar as [Benign]. Clinvar id is 1258939.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIP13	NM_004237.4	c.259-123G>T		intron_variant		ENST00000166345.8
TRIP13	NM_001166260.2	c.259-123G>T		intron_variant
TRIP13	XM_011514163.2	c.259-123G>T		intron_variant
TRIP13	XM_047417879.1	c.-201-123G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIP13	ENST00000166345.8	c.259-123G>T		intron_variant		1	NM_004237.4	P1
TRIP13	ENST00000512024.5	n.374-123G>T		intron_variant, non_coding_transcript_variant		1
TRIP13	ENST00000513435.1	c.246-123G>T		intron_variant		5
TRIP13	ENST00000508456.1	n.233-168G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0470 AC: 7143 AN: 152124 Hom.: 523 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0200

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00175

Gnomad OTH AF: 0.0406

GnomAD4 exome AF: 0.00703 AC: 6277 AN: 892860 Hom.: 373 AF XY: 0.00655 AC XY: 2908 AN XY: 444268

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.0120

Gnomad4 ASJ exome AF: 0.0141

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00110

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00188

Gnomad4 OTH exome AF: 0.0144

GnomAD4 genome AF: 0.0471 AC: 7168 AN: 152242 Hom.: 525 Cov.: 32 AF XY: 0.0455 AC XY: 3388 AN XY: 74436

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.0199

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00175

Gnomad4 OTH AF: 0.0406

Alfa AF: 0.0145 Hom.: 27

Bravo AF: 0.0537

Asia WGS AF: 0.0100 AC: 36 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

Jun 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.9
Dann	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs7730877; hg19: chr5-896657;