chr1-186312564-T-G

Position:

• chr1-186312564-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003292.3(TPR):​c.*1407A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 787,338 control chromosomes in the GnomAD database, including 162,257 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 0.63 (30693 hom., cov: 32)
  • Exomes 𝑓: 0.64 (131564 hom.)
• Consequence: TPR NM_003292.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405

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]

PRG4 (HGNC:9364): (proteoglycan 4) The protein encoded by this gene is a large proteoglycan that is synthesized by chondrocytes located at the surface of articular cartilage and by some synovial lining cells. This protein contains both chondroitin sulfate and keratan sulfate glycosaminoglycans. It functions as a boundary lubricant at the cartilage surface and contributes to the elastic absorption and energy dissipation of synovial fluid. Mutations in this gene result in camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPR	NM_003292.3	c.*1407A>C		3_prime_UTR_variant	51/51	ENST00000367478.9	NP_003283.2
PRG4	NM_005807.6	c.3991+192T>G		intron_variant		ENST00000445192.7	NP_005798.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPR	ENST00000367478.9	c.*1407A>C		3_prime_UTR_variant	51/51	1	NM_003292.3	ENSP00000356448	P1
PRG4	ENST00000445192.7	c.3991+192T>G		intron_variant		5	NM_005807.6	ENSP00000399679	P2

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96367 AN: 151854 Hom.: 30638 Cov.: 32

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.602

GnomAD4 exome AF: 0.641 AC: 407486 AN: 635364 Hom.: 131564 Cov.: 8 AF XY: 0.637 AC XY: 208806 AN XY: 327770

Gnomad4 AFR exome AF: 0.631

Gnomad4 AMR exome AF: 0.594

Gnomad4 ASJ exome AF: 0.547

Gnomad4 EAS exome AF: 0.670

Gnomad4 SAS exome AF: 0.549

Gnomad4 FIN exome AF: 0.651

Gnomad4 NFE exome AF: 0.656

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.635 AC: 96475 AN: 151974 Hom.: 30693 Cov.: 32 AF XY: 0.634 AC XY: 47076 AN XY: 74276

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.647

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.653

Gnomad4 OTH AF: 0.605

Alfa AF: 0.642 Hom.: 53851

Bravo AF: 0.632

Asia WGS AF: 0.645 AC: 2240 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.87
DANN	Benign	0.47

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: rs7756; hg19: chr1-186281696; COSMIC: COSV104422618; COSMIC: COSV104422618;