dbSNP rs1451340967: KPNA1:p.Ser387Thr (chr3-122433751-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002264.4(KPNA1):c.1160G>C(p.Ser387Thr) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S387N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

KPNA1
NM_002264.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

Publications

0 publications found

Variant links:

Genes affected

KPNA1 (HGNC:6394): (karyopherin subunit alpha 1) 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. This protein interacts with the recombination activating gene 1 (RAG1) protein and is a putative substrate of the RAG1 ubiquitin ligase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

KPNA1 links:

WDR5B-DT (HGNC:55192): (WDR5B divergent transcript)

WDR5B-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 (MetaRNN=0.114491165).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002264.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KPNA1	NM_002264.4	MANE Select	c.1160G>C	p.Ser387Thr	missense	Exon 12 of 14	NP_002255.3	P52294
KPNA1	NR_026698.2		n.1471G>C		non_coding_transcript_exon	Exon 13 of 15
WDR5B-DT	NR_125405.1		n.100+1230C>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KPNA1	ENST00000344337.11	TSL:1 MANE Select	c.1160G>C	p.Ser387Thr	missense	Exon 12 of 14	ENSP00000343701.6	P52294
KPNA1	ENST00000911570.1		c.1160G>C	p.Ser387Thr	missense	Exon 12 of 14	ENSP00000581629.1
KPNA1	ENST00000911571.1		c.1160G>C	p.Ser387Thr	missense	Exon 11 of 13	ENSP00000581630.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.11

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.84

M_CAP

Benign

0.0088

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

1.0

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.88

REVEL

Benign

0.066

Sift

Benign

0.21

Sift4G

Benign

0.30

Polyphen

0.0

Vest4

0.088

MutPred

0.39

Gain of catalytic residue at S387 (P = 0.1214)

MVP

0.48

MPC

0.81

ClinPred

0.20

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.058

Mutation Taster

=73/27

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over