rs13239597

Variant names:

• chr7-129055929-C-A
• rs13239597
• ENST00000635637.1:n.707C>A

Variant summary

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

The ENST00000635637.1(TPI1P2):​n.707C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 646,794 control chromosomes in the GnomAD database, including 4,747 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 0.090 (854 hom., cov: 32)
  • Exomes 𝑓: 0.11 (3893 hom.)
• Consequence: TPI1P2 ENST00000635637.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101
• Publications: 32 publications found

Genes affected

TPI1P2 (HGNC:):

TPI1P2 (HGNC:38069): (triosephosphate isomerase 1 pseudogene 2)

TNPO3 (HGNC:17103): (transportin 3) The protein encoded by this gene is a nuclear import receptor for serine/arginine-rich (SR) proteins such as the splicing factors SFRS1 and SFRS2. The encoded protein has also been shown to be involved in HIV-1 infection, apparently through interaction with the HIV-1 capsid protein. Several protein-coding and non-coding transcript variants have been found for this gene. [provided by RefSeq, Apr 2020]

TNPO3 Gene-Disease associations (from GenCC):

• autosomal dominant limb-girdle muscular dystrophy type 1F

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000635637.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPI1P2	NR_002187.3		n.707C>A		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPI1P2	ENST00000635637.1	TSL:6	n.707C>A		non_coding_transcript_exon	Exon 1 of 1
	TPI1P2	ENST00000491343.2	TSL:6	n.-90C>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0902 AC: 13725 AN: 152200 Hom.: 857 Cov.: 32

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.114 AC: 56551 AN: 494476 Hom.: 3893 Cov.: 4 AF XY: 0.116 AC XY: 30605 AN XY: 264160

African (AFR) AF: 0.0243 AC: 318 AN: 13110

American (AMR) AF: 0.185 AC: 4114 AN: 22274

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 1781 AN: 15774

East Asian (EAS) AF: 0.000159 AC: 5 AN: 31402

South Asian (SAS) AF: 0.159 AC: 8374 AN: 52802

European-Finnish (FIN) AF: 0.148 AC: 6539 AN: 44126

Middle Eastern (MID) AF: 0.123 AC: 365 AN: 2966

European-Non Finnish (NFE) AF: 0.112 AC: 32010 AN: 284730

Other (OTH) AF: 0.112 AC: 3045 AN: 27292

GnomAD4 genome AF: 0.0901 AC: 13719 AN: 152318 Hom.: 854 Cov.: 32 AF XY: 0.0927 AC XY: 6900 AN XY: 74472

African (AFR) AF: 0.0241 AC: 1002 AN: 41586

American (AMR) AF: 0.136 AC: 2087 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 396 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5188

South Asian (SAS) AF: 0.153 AC: 741 AN: 4830

European-Finnish (FIN) AF: 0.145 AC: 1539 AN: 10596

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7661 AN: 68028

Other (OTH) AF: 0.101 AC: 213 AN: 2112

Alfa AF: 0.0993 Hom.: 1538

Bravo AF: 0.0864

Asia WGS AF: 0.0580 AC: 202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.3
DANN	Benign	0.74
PhyloP100		0.10

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13239597; hg19: chr7-128695983;