1-186335166-C-T

Variant names:

• chr1-186335166-C-T
• rs3817586
• NM_003292.3:c.4912-37G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003292.3(TPR):​c.4912-37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,582,326 control chromosomes in the GnomAD database, including 11,183 homozygotes. 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: 𝑓 0.091 (965 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10218 hom.)
• Consequence: TPR NM_003292.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.958
• Publications: 12 publications found

Genes affected

TPR (HGNC:12017): (translocated promoter region, nuclear basket protein) This gene encodes a large coiled-coil protein that forms intranuclear filaments attached to the inner surface of nuclear pore complexes (NPCs). The protein directly interacts with several components of the NPC. It is required for the nuclear export of mRNAs and some proteins. Oncogenic fusions of the 5' end of this gene with several different kinase genes occur in some neoplasias. [provided by RefSeq, Jul 2008]

TPR Gene-Disease associations (from GenCC):

• intellectual developmental disorder, autosomal recessive 79

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003292.3. 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
	TPR	NM_003292.3	MANE Select	c.4912-37G>A		intron	N/A	NP_003283.2	P12270-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPR	ENST00000367478.9	TSL:1 MANE Select	c.4912-37G>A		intron	N/A	ENSP00000356448.3	P12270-1

Frequencies

GnomAD3 genomes AF: 0.0915 AC: 13897 AN: 151958 Hom.: 965 Cov.: 32

Gnomad AFR AF: 0.0304

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0936

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0958

Gnomad OTH AF: 0.108

GnomAD2 exomes AF: 0.119 AC: 27100 AN: 227244 AF XY: 0.120

Gnomad AFR exome AF: 0.0275

Gnomad AMR exome AF: 0.0876

Gnomad ASJ exome AF: 0.0934

Gnomad EAS exome AF: 0.397

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.0991

Gnomad OTH exome AF: 0.110

GnomAD4 exome AF: 0.106 AC: 151759 AN: 1430250 Hom.: 10218 Cov.: 29 AF XY: 0.106 AC XY: 75492 AN XY: 710172

African (AFR) AF: 0.0259 AC: 818 AN: 31530

American (AMR) AF: 0.0887 AC: 3350 AN: 37788

Ashkenazi Jewish (ASJ) AF: 0.0877 AC: 2165 AN: 24686

East Asian (EAS) AF: 0.404 AC: 15954 AN: 39468

South Asian (SAS) AF: 0.116 AC: 9526 AN: 81828

European-Finnish (FIN) AF: 0.110 AC: 5748 AN: 52244

Middle Eastern (MID) AF: 0.0532 AC: 298 AN: 5598

European-Non Finnish (NFE) AF: 0.0977 AC: 107236 AN: 1098132

Other (OTH) AF: 0.113 AC: 6664 AN: 58976

GnomAD4 genome AF: 0.0913 AC: 13890 AN: 152076 Hom.: 965 Cov.: 32 AF XY: 0.0954 AC XY: 7091 AN XY: 74328

African (AFR) AF: 0.0303 AC: 1259 AN: 41498

American (AMR) AF: 0.102 AC: 1556 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0936 AC: 325 AN: 3472

East Asian (EAS) AF: 0.381 AC: 1969 AN: 5162

South Asian (SAS) AF: 0.125 AC: 599 AN: 4810

European-Finnish (FIN) AF: 0.116 AC: 1224 AN: 10584

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0957 AC: 6508 AN: 67980

Other (OTH) AF: 0.109 AC: 230 AN: 2110

Alfa AF: 0.0965 Hom.: 1394

Bravo AF: 0.0880

Asia WGS AF: 0.253 AC: 880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.68
PhyloP100		-0.96
Mutation Taster		=100/0	polymorphism (auto)

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: rs3817586; hg19: chr1-186304298; COSMIC: COSV66601622; COSMIC: COSV66601622;