7-99195159-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001145715.3(KPNA7):c.464G>C(p.Gly155Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,551,590 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0054 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 14 hom. )

Consequence

KPNA7
NM_001145715.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.130

Publications

4 publications found

Variant links:

Genes affected

KPNA7 (HGNC:21839): (karyopherin subunit alpha 7) 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, but exhibits different nuclear localization signal binding specificity compared to other members of the family. A pseudogene of this gene has been defined on chromosome 5. [provided by RefSeq, Jul 2016]

KPNA7 Gene-Disease associations (from GenCC):

oocyte/zygote/embryo maturation arrest 17
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
partial corpus callosum agenesis-cerebellar vermis hypoplasia with posterior fossa cysts syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

KPNA7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01079914).

BP6

Variant 7-99195159-C-G is Benign according to our data. Variant chr7-99195159-C-G is described in ClinVar as Benign. ClinVar VariationId is 415825.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00541 (824/152182) while in subpopulation AFR AF = 0.0193 (803/41514). AF 95% confidence interval is 0.0182. There are 5 homozygotes in GnomAd4. There are 417 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KPNA7	NM_001145715.3 link	c.464G>C	p.Gly155Ala	missense_variant	Exon 5 of 11	ENST00000327442.7	NP_001139187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KPNA7	ENST00000327442.7 link	c.464G>C	p.Gly155Ala	missense_variant	Exon 5 of 11	1	NM_001145715.3	ENSP00000330878.6
KPNA7	ENST00000681060.1 link	c.464G>C	p.Gly155Ala	missense_variant	Exon 5 of 11			ENSP00000506489.1

Frequencies

GnomAD3 genomes

AF:

0.00541

AC:

822

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000984

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00102

AC:

159

AN:

156108

AF XY:

0.000895

show subpopulations

Gnomad AFR exome

AF:

0.0160

Gnomad AMR exome

AF:

0.00109

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000183

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000685

GnomAD4 exome

AF:

0.000604

AC:

845

AN:

1399408

Hom.:

Cov.:

AF XY:

0.000491

AC XY:

339

AN XY:

690210

show subpopulations

African (AFR)

AF:

0.0220

AC:

694

AN:

31598

American (AMR)

AF:

0.00106

AC:

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.000588

AC:

AN:

35736

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49276

Middle Eastern (MID)

AF:

0.000351

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.0000334

AC:

AN:

1078976

Other (OTH)

AF:

0.000914

AC:

AN:

58002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

116

175

233

291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00541

AC:

824

AN:

152182

Hom.:

Cov.:

AF XY:

0.00561

AC XY:

417

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0193

AC:

803

AN:

41514

American (AMR)

AF:

0.000982

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68028

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

116

155

194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000771

Hom.:

Bravo

AF:

0.00619

ESP6500AA

AF:

0.0188

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00179

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

6.7

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0079

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.10

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.41

PhyloP100

-0.13

PrimateAI

Benign

0.27

PROVEAN

Benign

-2.1

REVEL

Benign

0.15

Sift

Benign

0.82

Sift4G

Benign

1.0

Polyphen

0.99

Vest4

0.16

MVP

0.061

ClinPred

0.025

GERP RS

-0.29

Varity_R

0.049

gMVP

0.14

Mutation Taster

=99/1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over