3-160535900-T-A

Position:

• chr3-160535900-T-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002268.5(KPNA4):​c.115-3A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 9)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: KPNA4 NM_002268.5 splice_region, intron
• Scores: Splicing: ADA: 0.00004280
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.719

Genes affected

KPNA4 (HGNC:6397): (karyopherin subunit alpha 4) The nuclear import of karyophilic proteins is directed by short amino acid sequences termed nuclear localization signals (NLSs). Karyopherins, or importins, are cytoplasmic proteins that recognize NLSs and dock NLS-containing proteins to the nuclear pore complex. The protein encoded by this gene shares the sequence similarity with Xenopus importin-alpha and Saccharomyces cerevisiae Srp1. This protein is found to interact with the NLSs of DNA helicase Q1 and SV40 T antigen. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-160535900-T-A is Benign according to our data. Variant chr3-160535900-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2654259.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KPNA4	NM_002268.5	c.115-3A>T		splice_region_variant, intron_variant		ENST00000334256.9	NP_002259.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KPNA4	ENST00000334256.9	c.115-3A>T		splice_region_variant, intron_variant		1	NM_002268.5	ENSP00000334373.4

Frequencies

GnomAD3 genomes AF: 0.000240 AC: 16 AN: 66534 Hom.: 0 Cov.: 9

Gnomad AFR AF: 0.000176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000194

Gnomad ASJ AF: 0.000497

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000304

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000270 AC: 7 AN: 258826 Hom.: 0 Cov.: 6 AF XY: 0.0000320 AC XY: 4 AN XY: 124918

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000398

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000164

Gnomad4 NFE exome AF: 0.0000235

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.000240 AC: 16 AN: 66536 Hom.: 0 Cov.: 9 AF XY: 0.000135 AC XY: 4 AN XY: 29612

Gnomad4 AFR AF: 0.000175

Gnomad4 AMR AF: 0.000194

Gnomad4 ASJ AF: 0.000497

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000304

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00118 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

KPNA4: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000043
dbscSNV1_RF	Benign	0.0
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

LitVar

Other links and lift over

dbSNP: rs1421471586; hg19: chr3-160253688;