rs184436527

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-893106-C-G
• chr5-893106-C-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>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,575,386 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00065 (9 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=-0.42).
• BP6: Variant 5-893106-C-G is Benign according to our data. Variant chr5-893106-C-G is described in ClinVar as Benign. ClinVar VariationId is 2806097.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00627 (954/152210) while in subpopulation AFR AF = 0.0222 (924/41546). AF 95% confidence interval is 0.0211. There are 7 homozygotes in GnomAd4. There are 398 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 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>G		intron	N/A	NP_004228.1	Q15645-1
	TRIP13	NM_001166260.2		c.92+16C>G		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>G		intron	N/A	ENSP00000166345.3	Q15645-1
	TRIP13	ENST00000512024.5	TSL:1	n.207+16C>G		intron	N/A
	TRIP13	ENST00000891004.1		c.92+16C>G		intron	N/A	ENSP00000561063.1

Frequencies

GnomAD3 genomes AF: 0.00627 AC: 953 AN: 152092 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00126 AC: 231 AN: 183102 AF XY: 0.000997

Gnomad AFR exome AF: 0.0196

Gnomad AMR exome AF: 0.000490

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000818

GnomAD4 exome AF: 0.000648 AC: 922 AN: 1423176 Hom.: 9 Cov.: 31 AF XY: 0.000564 AC XY: 398 AN XY: 705790

African (AFR) AF: 0.0229 AC: 754 AN: 32936

American (AMR) AF: 0.000470 AC: 19 AN: 40448

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25448

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

South Asian (SAS) AF: 0.0000611 AC: 5 AN: 81842

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39896

Middle Eastern (MID) AF: 0.000352 AC: 2 AN: 5684

European-Non Finnish (NFE) AF: 0.0000164 AC: 18 AN: 1099206

Other (OTH) AF: 0.00208 AC: 123 AN: 59246

GnomAD4 genome AF: 0.00627 AC: 954 AN: 152210 Hom.: 7 Cov.: 32 AF XY: 0.00535 AC XY: 398 AN XY: 74414

African (AFR) AF: 0.0222 AC: 924 AN: 41546

American (AMR) AF: 0.000981 AC: 15 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67976

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.000364 Hom.: 1

Bravo AF: 0.00695

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	-0.42
CADD	Benign	6.7
DANN	Benign	0.32
PhyloP100		1.0
PromoterAI		0.044	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)		0.010		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;