rs148885407

Variant names:

• chr7-129005130-A-C
• NM_012470.4:c.582T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-129005130-A-C
• chr7-129005130-A-G
• chr7-129005130-A-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_012470.4(TNPO3):​c.582T>G​(p.Asp194Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: TNPO3 NM_012470.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19914818).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNPO3	NM_012470.4	c.582T>G	p.Asp194Glu	missense_variant	Exon 5 of 23	ENST00000265388.10	NP_036602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNPO3	ENST00000265388.10	c.582T>G	p.Asp194Glu	missense_variant	Exon 5 of 23	1	NM_012470.4	ENSP00000265388.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461610 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727094

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T;T;T;.;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.070
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.79	T;T;T;T;.
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.20	T;T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.1	M;.;.;M;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.2	N;.;N;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.010	D;.;D;D;D
Sift4G	Uncertain	0.015	D;D;D;D;D
Polyphen		0.18	B;P;.;.;P
Vest4		0.11
MutPred		0.35		Gain of disorder (P = 0.0852);Gain of disorder (P = 0.0852);.;Gain of disorder (P = 0.0852);Gain of disorder (P = 0.0852);
MVP		0.65
MPC		1.2
ClinPred		0.92	D
GERP RS		3.2
Varity_R		0.45
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-128645184;