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_012470.4(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_012470.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436

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]

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNPO3	NM_012470.4	c.*1288A>G		downstream_gene_variant		ENST00000265388.10	NP_036602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNPO3	ENST00000265388.10	c.*1288A>G		downstream_gene_variant		1	NM_012470.4	ENSP00000265388.5
TNPO3	ENST00000627585.2	c.*1288A>G		downstream_gene_variant		2		ENSP00000487231.1

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

Gnomad4 AFR exome AC: 0 AN: 0

Gnomad4 AMR exome AC: 0 AN: 0

Gnomad4 ASJ exome AC: 0 AN: 0

Gnomad4 EAS exome AC: 0 AN: 0

Gnomad4 SAS exome AC: 0 AN: 0

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 2

Gnomad4 NFE exome AF: 0.500 AC: 2 AN: 4

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.0244 AC: 0.0243662 AN: 0.0243662

Gnomad4 AMR AF: 0.138 AC: 0.137724 AN: 0.137724

Gnomad4 ASJ AF: 0.114 AC: 0.114187 AN: 0.114187

Gnomad4 EAS AF: 0.00193 AC: 0.00192678 AN: 0.00192678

Gnomad4 SAS AF: 0.153 AC: 0.153002 AN: 0.153002

Gnomad4 FIN AF: 0.145 AC: 0.144863 AN: 0.144863

Gnomad4 NFE AF: 0.112 AC: 0.112457 AN: 0.112457

Gnomad4 OTH AF: 0.101 AC: 0.101044 AN: 0.101044

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 v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10488631; hg19: chr7-128594183;