7-99185162-T-G

Position:

• chr7-99185162-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001145715.3(KPNA7):​c.901A>C​(p.Thr301Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: KPNA7 NM_001145715.3 missense, splice_region
• Scores: Splicing: ADA: 0.06393
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.45

Genes affected

KPNA7 (HGNC:21839): (karyopherin subunit alpha 7) The transport of molecules between the nucleus and the cytoplasm in eukaryotic cells is mediated by the nuclear pore complex (NPC), which consists of 60-100 proteins. Small molecules (up to 70 kD) can pass through the nuclear pore by nonselective diffusion while larger molecules are transported by an active process. The protein encoded by this gene belongs to the importin alpha family, and is involved in nuclear protein import, but exhibits different nuclear localization signal binding specificity compared to other members of the family. A pseudogene of this gene has been defined on chromosome 5. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KPNA7	NM_001145715.3	c.901A>C	p.Thr301Pro	missense_variant, splice_region_variant	8/11	ENST00000327442.7	NP_001139187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KPNA7	ENST00000327442.7	c.901A>C	p.Thr301Pro	missense_variant, splice_region_variant	8/11	1	NM_001145715.3	ENSP00000330878.6
KPNA7	ENST00000681060.1	c.901A>C	p.Thr301Pro	missense_variant, splice_region_variant	8/11			ENSP00000506489.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.079	T
Eigen	Uncertain	0.39
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Uncertain	0.20	D
MutationAssessor	Pathogenic	3.5	M
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.48
MutPred		0.66		Gain of catalytic residue at T301 (P = 0.0619);
MVP		0.44
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.93
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.064
dbscSNV1_RF	Benign	0.22
SpliceAI score (max)		0.12		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: chr7-98782785;