rs11932

Variant names:

• chr3-122422288-C-T
• rs11932
• NM_002264.4:c.*4697G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002264.4(KPNA1):​c.*4697G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 147,930 control chromosomes in the GnomAD database, including 1,820 homozygotes. 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: 𝑓 0.15 (1820 hom., cov: 29)
  • Failed GnomAD Quality Control
• Consequence: KPNA1 NM_002264.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662
• Publications: 12 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KPNA1	NM_002264.4	MANE Select	c.*4697G>A		3_prime_UTR	Exon 14 of 14	NP_002255.3	P52294
	KPNA1	NR_026698.2		n.6625G>A		non_coding_transcript_exon	Exon 15 of 15
	WDR5B-DT	NR_125405.1		n.45+6038C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KPNA1	ENST00000344337.11	TSL:1 MANE Select	c.*4697G>A		3_prime_UTR	Exon 14 of 14	ENSP00000343701.6	P52294
	KPNA1	ENST00000911570.1		c.*4697G>A		3_prime_UTR	Exon 14 of 14	ENSP00000581629.1
	WDR5B-DT	ENST00000608015.1	TSL:5	n.27-3319C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.154 AC: 22764 AN: 147838 Hom.: 1811 Cov.: 29

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.0971

Gnomad ASJ AF: 0.0893

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.103

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.150

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.154 AC: 22787 AN: 147930 Hom.: 1820 Cov.: 29 AF XY: 0.153 AC XY: 10987 AN XY: 71742

African (AFR) AF: 0.179 AC: 7160 AN: 39950

American (AMR) AF: 0.0970 AC: 1407 AN: 14510

Ashkenazi Jewish (ASJ) AF: 0.0893 AC: 310 AN: 3470

East Asian (EAS) AF: 0.327 AC: 1657 AN: 5068

South Asian (SAS) AF: 0.108 AC: 504 AN: 4678

European-Finnish (FIN) AF: 0.151 AC: 1432 AN: 9504

Middle Eastern (MID) AF: 0.104 AC: 29 AN: 280

European-Non Finnish (NFE) AF: 0.145 AC: 9811 AN: 67522

Other (OTH) AF: 0.153 AC: 312 AN: 2044

Alfa AF: 0.152 Hom.: 5648

Bravo AF: 0.153

Asia WGS AF: 0.225 AC: 784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.62
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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: rs11932; hg19: chr3-122141135;