chr5-893106-C-T

Variant names:

• chr5-893106-C-T
• rs184436527
• NM_004237.4:c.92+16C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_004237.4(TRIP13):​c.92+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0096 in 1,575,356 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0099 (107 hom.)
• Consequence: TRIP13 NM_004237.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.00
• Publications: 1 publications found

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]

TRIP13 Gene-Disease associations (from GenCC):

• mosaic variegated aneuploidy syndrome 3

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• oocyte maturation defect 9

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• female infertility due to oocyte meiotic arrest

  Inheritance: AR Classification: MODERATE Submitted by: Franklin by Genoox
• kidney Wilms tumor

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• mosaic variegated aneuploidy syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 5-893106-C-T is Benign according to our data. Variant chr5-893106-C-T is described in ClinVar as Benign. ClinVar VariationId is 2801949.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00632 (962/152210) while in subpopulation SAS AF = 0.0112 (54/4824). AF 95% confidence interval is 0.00959. There are 3 homozygotes in GnomAd4. There are 454 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004237.4. 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
	TRIP13	NM_004237.4	MANE Select	c.92+16C>T		intron	N/A	NP_004228.1	Q15645-1
	TRIP13	NM_001166260.2		c.92+16C>T		intron	N/A	NP_001159732.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIP13	ENST00000166345.8	TSL:1 MANE Select	c.92+16C>T		intron	N/A	ENSP00000166345.3	Q15645-1
	TRIP13	ENST00000512024.5	TSL:1	n.207+16C>T		intron	N/A
	TRIP13	ENST00000891004.1		c.92+16C>T		intron	N/A	ENSP00000561063.1

Frequencies

GnomAD3 genomes AF: 0.00633 AC: 962 AN: 152092 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.00480

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00834 AC: 1527 AN: 183102 AF XY: 0.00889

Gnomad AFR exome AF: 0.00185

Gnomad AMR exome AF: 0.00238

Gnomad ASJ exome AF: 0.0120

Gnomad EAS exome AF: 0.0000680

Gnomad FIN exome AF: 0.00555

Gnomad NFE exome AF: 0.0112

Gnomad OTH exome AF: 0.00634

GnomAD4 exome AF: 0.00995 AC: 14158 AN: 1423146 Hom.: 107 Cov.: 31 AF XY: 0.0100 AC XY: 7064 AN XY: 705772

African (AFR) AF: 0.00137 AC: 45 AN: 32942

American (AMR) AF: 0.00247 AC: 100 AN: 40446

Ashkenazi Jewish (ASJ) AF: 0.0122 AC: 310 AN: 25448

East Asian (EAS) AF: 0.0000260 AC: 1 AN: 38470

South Asian (SAS) AF: 0.0133 AC: 1085 AN: 81840

European-Finnish (FIN) AF: 0.00567 AC: 226 AN: 39894

Middle Eastern (MID) AF: 0.00774 AC: 44 AN: 5684

European-Non Finnish (NFE) AF: 0.0107 AC: 11793 AN: 1099178

Other (OTH) AF: 0.00935 AC: 554 AN: 59244

GnomAD4 genome AF: 0.00632 AC: 962 AN: 152210 Hom.: 3 Cov.: 32 AF XY: 0.00610 AC XY: 454 AN XY: 74414

African (AFR) AF: 0.00195 AC: 81 AN: 41546

American (AMR) AF: 0.00183 AC: 28 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5158

South Asian (SAS) AF: 0.0112 AC: 54 AN: 4824

European-Finnish (FIN) AF: 0.00480 AC: 51 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0102 AC: 695 AN: 67976

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00433 Hom.: 1

Bravo AF: 0.00567

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	6.7
DANN	Benign	0.65
PhyloP100		1.0
PromoterAI		0.056	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	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: rs184436527; hg19: chr5-893221;