rs10488631

Variant names:

• chr7-128954129-T-C
• rs10488631
• NM_012470.4:c.*1288A>G

Variant summary

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

The NM_001382216.1(TNPO3):​c.*1288A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0902 in 152,324 control chromosomes in the GnomAD database, including 860 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 (860 hom., cov: 33)
  • Exomes 𝑓: 0.33 (0 hom.)
• Consequence: TNPO3 NM_001382216.1 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436
• Publications: 197 publications found

Genes affected

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=-0.84).
• 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: NM_001382216.1. 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
	TNPO3	NM_012470.4	MANE Select	c.*1288A>G		downstream_gene	N/A	NP_036602.1
	TNPO3	NM_001382216.1		c.*1288A>G		downstream_gene	N/A	NP_001369145.1
	TNPO3	NM_001382217.1		c.*1288A>G		downstream_gene	N/A	NP_001369146.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNPO3	ENST00000265388.10	TSL:1 MANE Select	c.*1288A>G		downstream_gene	N/A	ENSP00000265388.5
	TNPO3	ENST00000627585.2	TSL:2	c.*1288A>G		downstream_gene	N/A	ENSP00000487231.1
	TNPO3	ENST00000929007.1		c.*1288A>G		downstream_gene	N/A	ENSP00000599066.1

Frequencies

GnomAD3 genomes AF: 0.0903 AC: 13741 AN: 152200 Hom.: 863 Cov.: 33

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.138

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: 0.112

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.333 AC: 2 AN: 6 Hom.: 0 AF XY: 0.333 AC XY: 2 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0902 AC: 13736 AN: 152318 Hom.: 860 Cov.: 33 AF XY: 0.0929 AC XY: 6918 AN XY: 74484

African (AFR) AF: 0.0244 AC: 1013 AN: 41574

American (AMR) AF: 0.138 AC: 2108 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 396 AN: 3468

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5190

South Asian (SAS) AF: 0.153 AC: 739 AN: 4830

European-Finnish (FIN) AF: 0.145 AC: 1537 AN: 10610

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

European-Non Finnish (NFE) AF: 0.112 AC: 7650 AN: 68026

Other (OTH) AF: 0.101 AC: 213 AN: 2108

Alfa AF: 0.104 Hom.: 4099

Bravo AF: 0.0868

Asia WGS AF: 0.0590 AC: 204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.8
DANN	Benign	0.65
PhyloP100		-0.44

Splicing

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

Other links and lift over

dbSNP: rs10488631; hg19: chr7-128594183;