2-183158306-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_138285.5(NUP35):c.633G>A(p.Met211Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00001 in 1,597,834 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000090 ( 0 hom. )
Consequence
NUP35
NM_138285.5 missense
NM_138285.5 missense
Scores
6
5
6
Clinical Significance
Conservation
PhyloP100: 9.59
Genes affected
NUP35 (HGNC:29797): (nucleoporin 35) This gene encodes a member of the nucleoporin family. The encoded protein contains two membrane binding regions, is localized to the nuclear rim, and is part of the nuclear pore complex. All molecules entering or leaving the nucleus either diffuse through or are actively transported by the nuclear pore complex. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene have been defined on chromosomes 7 and 10. [provided by RefSeq, Dec 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NUP35 | NM_138285.5 | c.633G>A | p.Met211Ile | missense_variant | 7/9 | ENST00000295119.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NUP35 | ENST00000295119.9 | c.633G>A | p.Met211Ile | missense_variant | 7/9 | 1 | NM_138285.5 | P1 | |
NUP35 | ENST00000409798.5 | c.582G>A | p.Met194Ile | missense_variant | 8/10 | 2 | |||
NUP35 | ENST00000479162.5 | n.530G>A | non_coding_transcript_exon_variant | 6/7 | 2 | ||||
NUP35 | ENST00000374930.7 | c.*32G>A | 3_prime_UTR_variant, NMD_transcript_variant | 6/8 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152130Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000821 AC: 2AN: 243470Hom.: 0 AF XY: 0.00000759 AC XY: 1AN XY: 131698
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GnomAD4 exome AF: 0.00000899 AC: 13AN: 1445704Hom.: 0 Cov.: 29 AF XY: 0.00000834 AC XY: 6AN XY: 719024
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74320
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 06, 2021 | The c.633G>A (p.M211I) alteration is located in exon 7 (coding exon 7) of the NUP35 gene. This alteration results from a G to A substitution at nucleotide position 633, causing the methionine (M) at amino acid position 211 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
D;T
Sift4G
Benign
T;T
Polyphen
0.75
.;P
Vest4
MutPred
0.67
.;Loss of MoRF binding (P = 0.0881);
MVP
MPC
0.73
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at