chr5-72848388-A-T

Position:

• chr5-72848388-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002270.4(TNPO1):​c.19A>T​(p.Thr7Ser) variant causes a missense 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: TNPO1 NM_002270.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.12

Genes affected

TNPO1 (HGNC:6401): (transportin 1) This gene encodes the beta subunit of the karyopherin receptor complex which interacts with nuclear localization signals to target nuclear proteins to the nucleus. The karyopherin receptor complex is a heterodimer of an alpha subunit which recognizes the nuclear localization signal and a beta subunit which docks the complex at nucleoporins. Alternate splicing of this gene results in several transcript variants encoding different proteins. [provided by RefSeq, Jun 2018]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.064696014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNPO1	NM_002270.4	c.19A>T	p.Thr7Ser	missense_variant	2/25	ENST00000337273.10	NP_002261.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNPO1	ENST00000337273.10	c.19A>T	p.Thr7Ser	missense_variant	2/25	1	NM_002270.4	ENSP00000336712.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 20, 2023

The c.19A>T (p.T7S) alteration is located in exon 2 (coding exon 2) of the TNPO1 gene. This alteration results from a A to T substitution at nucleotide position 19, causing the threonine (T) at amino acid position 7 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	20
DANN	Benign	0.90
DEOGEN2	Benign	0.084	T;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.065	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PROVEAN	Benign	-0.31	N;N
REVEL	Benign	0.037
Sift	Benign	0.61	T;T
Sift4G	Benign	0.44	T;T
Polyphen		0.0	B;B
Vest4		0.14
MutPred		0.18		Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP		0.36
MPC		0.91
ClinPred		0.092	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.051

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-72144215;