5-893100-A-G

Variant names:

• chr5-893100-A-G
• rs376619779
• NM_004237.4:c.92+10A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_004237.4(TRIP13):​c.92+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,581,206 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: TRIP13 NM_004237.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.14
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 5-893100-A-G is Benign according to our data. Variant chr5-893100-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3659923.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.000122 (175/1429246) while in subpopulation AMR AF = 0.000386 (16/41470). AF 95% confidence interval is 0.000241. There are 1 homozygotes in GnomAdExome4. There are 80 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

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+10A>G		intron	N/A	NP_004228.1	Q15645-1
	TRIP13	NM_001166260.2		c.92+10A>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+10A>G		intron	N/A	ENSP00000166345.3	Q15645-1
	TRIP13	ENST00000512024.5	TSL:1	n.207+10A>G		intron	N/A
	TRIP13	ENST00000891004.1		c.92+10A>G		intron	N/A	ENSP00000561063.1

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 151842 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000151 AC: 29 AN: 191828 AF XY: 0.000124

Gnomad AFR exome AF: 0.0000884

Gnomad AMR exome AF: 0.000472

Gnomad ASJ exome AF: 0.000113

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000128

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000122 AC: 175 AN: 1429246 Hom.: 1 Cov.: 31 AF XY: 0.000113 AC XY: 80 AN XY: 709180

African (AFR) AF: 0.0000908 AC: 3 AN: 33026

American (AMR) AF: 0.000386 AC: 16 AN: 41470

Ashkenazi Jewish (ASJ) AF: 0.000431 AC: 11 AN: 25528

East Asian (EAS) AF: 0.0000259 AC: 1 AN: 38680

South Asian (SAS) AF: 0.0000972 AC: 8 AN: 82312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40720

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5648

European-Non Finnish (NFE) AF: 0.000112 AC: 124 AN: 1102400

Other (OTH) AF: 0.000202 AC: 12 AN: 59462

GnomAD4 genome AF: 0.000151 AC: 23 AN: 151960 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74288

African (AFR) AF: 0.000169 AC: 7 AN: 41468

American (AMR) AF: 0.000262 AC: 4 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5136

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

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

European-Non Finnish (NFE) AF: 0.000133 AC: 9 AN: 67882

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.000155

ClinVar

ClinVar submissions

Significance: Likely 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	-0.61
CADD	Benign	2.2
DANN	Benign	0.14
PhyloP100		-4.1
PromoterAI		0.17	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs376619779; hg19: chr5-893215;