chr7-128970321-T-A

Variant names:

• chr7-128970321-T-A
• rs190759031
• NM_012470.4:c.2431-6A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012470.4(TNPO3):​c.2431-6A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNPO3 NM_012470.4 splice_region, intron
• Scores: Splicing: ADA: 0.6215
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.19).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNPO3	NM_012470.4	c.2431-6A>T		splice_region_variant, intron_variant	Intron 19 of 22	ENST00000265388.10	NP_036602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNPO3	ENST00000265388.10	c.2431-6A>T		splice_region_variant, intron_variant	Intron 19 of 22	1	NM_012470.4	ENSP00000265388.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1418324 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 700328

African (AFR) AF: 0.00 AC: 0 AN: 31842

American (AMR) AF: 0.00 AC: 0 AN: 37848

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23968

East Asian (EAS) AF: 0.00 AC: 0 AN: 39084

South Asian (SAS) AF: 0.00 AC: 0 AN: 80472

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5576

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088818

Other (OTH) AF: 0.00 AC: 0 AN: 58436

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
CADD	Benign	8.3
DANN	Benign	0.95
PhyloP100		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.62
dbscSNV1_RF	Benign	0.57
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: rs190759031; hg19: chr7-128610375;