9-131128416-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005085.4(NUP214):​c.326C>T​(p.Ala109Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,613,618 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0075 ( 13 hom., cov: 32)
Exomes 𝑓: 0.00080 ( 16 hom. )

Consequence

NUP214
NM_005085.4 missense

Scores

18

Clinical Significance

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

Conservation

PhyloP100: 2.23
Variant links:
Genes affected
NUP214 (HGNC:8064): (nucleoporin 214) The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells. This gene is a member of the FG-repeat-containing nucleoporins. The protein encoded by this gene is localized to the cytoplasmic face of the nuclear pore complex where it is required for proper cell cycle progression and nucleocytoplasmic transport. The 3' portion of this gene forms a fusion gene with the DEK gene on chromosome 6 in a t(6,9) translocation associated with acute myeloid leukemia and myelodysplastic syndrome. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0068000555).
BP6
Variant 9-131128416-C-T is Benign according to our data. Variant chr9-131128416-C-T is described in ClinVar as [Benign]. Clinvar id is 789780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-131128416-C-T is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00752 (1145/152224) while in subpopulation AFR AF= 0.0259 (1076/41526). AF 95% confidence interval is 0.0246. There are 13 homozygotes in gnomad4. There are 525 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NUP214NM_005085.4 linkc.326C>T p.Ala109Val missense_variant Exon 3 of 36 ENST00000359428.10 NP_005076.3 P35658-1
NUP214NM_001318324.2 linkc.326C>T p.Ala109Val missense_variant Exon 3 of 36 NP_001305253.1 P35658-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NUP214ENST00000359428.10 linkc.326C>T p.Ala109Val missense_variant Exon 3 of 36 1 NM_005085.4 ENSP00000352400.5 P35658-1

Frequencies

GnomAD3 genomes
AF:
0.00754
AC:
1147
AN:
152106
Hom.:
13
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0260
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00301
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00478
GnomAD3 exomes
AF:
0.00217
AC:
546
AN:
251270
Hom.:
10
AF XY:
0.00182
AC XY:
247
AN XY:
135806
show subpopulations
Gnomad AFR exome
AF:
0.0286
Gnomad AMR exome
AF:
0.00171
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000132
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000801
AC:
1170
AN:
1461394
Hom.:
16
Cov.:
31
AF XY:
0.000669
AC XY:
486
AN XY:
726972
show subpopulations
Gnomad4 AFR exome
AF:
0.0271
Gnomad4 AMR exome
AF:
0.00179
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000128
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000378
Gnomad4 OTH exome
AF:
0.00189
GnomAD4 genome
AF:
0.00752
AC:
1145
AN:
152224
Hom.:
13
Cov.:
32
AF XY:
0.00705
AC XY:
525
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.0259
Gnomad4 AMR
AF:
0.00301
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00473
Alfa
AF:
0.00148
Hom.:
2
Bravo
AF:
0.00907
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.0252
AC:
111
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00278
AC:
338
Asia WGS
AF:
0.00318
AC:
11
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.044
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
14
DANN
Benign
0.78
DEOGEN2
Benign
0.14
T;.;T
Eigen
Benign
-0.95
Eigen_PC
Benign
-0.68
FATHMM_MKL
Benign
0.25
N
LIST_S2
Benign
0.77
T;T;T
MetaRNN
Benign
0.0068
T;T;T
MetaSVM
Benign
-0.84
T
MutationAssessor
Benign
-1.1
N;N;.
PrimateAI
Benign
0.33
T
PROVEAN
Benign
2.1
N;N;N
REVEL
Benign
0.20
Sift
Benign
1.0
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0010
B;B;.
Vest4
0.31
MVP
0.13
MPC
0.078
ClinPred
0.0027
T
GERP RS
2.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.060
gMVP
0.49

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.

Other links and lift over

dbSNP: rs58363837; hg19: chr9-134003803; API