Variant 3-122433726-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_002264.4(KPNA1):c.1185G>A(p.Arg395=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,613,390 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0086 ( 7 hom., cov: 33)

Exomes 𝑓: 0.012 ( 106 hom. )

Consequence

KPNA1
NM_002264.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.593

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 3-122433726-C-T is Benign according to our data. Variant chr3-122433726-C-T is described in ClinVar as [Benign]. Clinvar id is 774847.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.593 with no splicing effect.

BS2

High AC in GnomAd4 at 1315 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KPNA1	NM_002264.4 linkuse as main transcript	c.1185G>A	p.Arg395=	synonymous_variant	12/14	ENST00000344337.11
WDR5B-DT	NR_125405.1 linkuse as main transcript	n.100+1205C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KPNA1	ENST00000344337.11 linkuse as main transcript	c.1185G>A	p.Arg395=	synonymous_variant	12/14	1	NM_002264.4	P1
WDR5B-DT	ENST00000609469.5 linkuse as main transcript	n.99+1205C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00865

AC:

1316

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00251

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.0265

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00208

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0135

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00845

AC:

2121

AN:

250916

Hom.:

AF XY:

0.00868

AC XY:

1177

AN XY:

135630

show subpopulations

Gnomad AFR exome

AF:

0.00234

Gnomad AMR exome

AF:

0.00410

Gnomad ASJ exome

AF:

0.0266

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00406

Gnomad FIN exome

AF:

0.00273

Gnomad NFE exome

AF:

0.0126

Gnomad OTH exome

AF:

0.00947

GnomAD4 exome

AF:

0.0115

AC:

16876

AN:

1461170

Hom.:

106

Cov.:

AF XY:

0.0112

AC XY:

8140

AN XY:

726922

show subpopulations

Gnomad4 AFR exome

AF:

0.00185

Gnomad4 AMR exome

AF:

0.00464

Gnomad4 ASJ exome

AF:

0.0270

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00454

Gnomad4 FIN exome

AF:

0.00318

Gnomad4 NFE exome

AF:

0.0132

Gnomad4 OTH exome

AF:

0.0104

GnomAD4 genome

AF:

0.00864

AC:

1315

AN:

152220

Hom.:

Cov.:

AF XY:

0.00777

AC XY:

578

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00250

Gnomad4 AMR

AF:

0.00595

Gnomad4 ASJ

AF:

0.0265

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00208

Gnomad4 NFE

AF:

0.0135

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.00899

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0142

EpiControl

AF:

0.0138

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

7.2

DANN

Benign

0.62

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over