3-160509919-A-G

Variant names:

• chr3-160509919-A-G
• rs2305402
• NM_002268.5:c.1138-48T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002268.5(KPNA4):​c.1138-48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000965 in 1,036,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)
  • Exomes 𝑓: 9.7e-7 (0 hom.)
• Consequence: KPNA4 NM_002268.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002268.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KPNA4	NM_002268.5	MANE Select	c.1138-48T>C		intron	N/A	NP_002259.1	O00629

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KPNA4	ENST00000334256.9	TSL:1 MANE Select	c.1138-48T>C		intron	N/A	ENSP00000334373.4	O00629
	KPNA4	ENST00000960890.1		c.1138-48T>C		intron	N/A	ENSP00000630949.1
	KPNA4	ENST00000914241.1		c.1174-48T>C		intron	N/A	ENSP00000584300.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.65e-7 AC: 1 AN: 1036026 Hom.: 0 Cov.: 14 AF XY: 0.00000187 AC XY: 1 AN XY: 533698

African (AFR) AF: 0.00 AC: 0 AN: 24082

American (AMR) AF: 0.00 AC: 0 AN: 38776

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22770

East Asian (EAS) AF: 0.00 AC: 0 AN: 37660

South Asian (SAS) AF: 0.00 AC: 0 AN: 73866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4716

European-Non Finnish (NFE) AF: 0.00000136 AC: 1 AN: 735312

Other (OTH) AF: 0.00 AC: 0 AN: 45948

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.94
PhyloP100		2.0

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

Other links and lift over

dbSNP: rs2305402; hg19: chr3-160227707;