chr18-12986873-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001013437.2(SEH1L):c.1082C>T(p.Thr361Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000051 in 1,567,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000035 ( 0 hom. )
Consequence
SEH1L
NM_001013437.2 missense
NM_001013437.2 missense
Scores
3
13
Clinical Significance
Conservation
PhyloP100: 5.03
Genes affected
SEH1L (HGNC:30379): (SEH1 like nucleoporin) The protein encoded by this gene is part of a nuclear pore complex, Nup107-160. This protein contains WD repeats and shares 34% amino acid identity with yeast Seh1 and 30% identity with yeast Sec13. All constituents of the Nup107-160 complex, including this protein, specifically localize to kinetochores in mitosis. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1513187).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEH1L | NM_001013437.2 | c.1082C>T | p.Thr361Ile | missense_variant | 9/9 | ENST00000399892.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEH1L | ENST00000399892.7 | c.1082C>T | p.Thr361Ile | missense_variant | 9/9 | 1 | NM_001013437.2 | P3 | |
SEH1L | ENST00000262124.15 | c.*1621C>T | 3_prime_UTR_variant | 9/9 | 1 | A1 | |||
SEH1L | ENST00000590843.1 | n.4548C>T | non_coding_transcript_exon_variant | 4/4 | 1 | ||||
CEP192-DT | ENST00000588211.1 | n.266+1G>A | splice_donor_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000199 AC: 3AN: 150624Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.00000353 AC: 5AN: 1417032Hom.: 0 Cov.: 32 AF XY: 0.00000568 AC XY: 4AN XY: 704122
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GnomAD4 genome AF: 0.0000199 AC: 3AN: 150624Hom.: 0 Cov.: 31 AF XY: 0.0000136 AC XY: 1AN XY: 73396
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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 | May 27, 2022 | The c.1082C>T (p.T361I) alteration is located in exon 9 (coding exon 9) of the SEH1L gene. This alteration results from a C to T substitution at nucleotide position 1082, causing the threonine (T) at amino acid position 361 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of phosphorylation at T361 (P = 0.036);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
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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