18-12963363-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001013437.2(SEH1L):​c.513C>A​(p.Asn171Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SEH1L
NM_001013437.2 missense

Scores

3
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18
Variant links:
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SEH1LNM_001013437.2 linkc.513C>A p.Asn171Lys missense_variant Exon 4 of 9 ENST00000399892.7 NP_001013455.1 Q96EE3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SEH1LENST00000399892.7 linkc.513C>A p.Asn171Lys missense_variant Exon 4 of 9 1 NM_001013437.2 ENSP00000382779.1 Q96EE3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 05, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.513C>A (p.N171K) alteration is located in exon 4 (coding exon 4) of the SEH1L gene. This alteration results from a C to A substitution at nucleotide position 513, causing the asparagine (N) at amino acid position 171 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Uncertain
0.090
D
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.29
T;.;.;T;T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.95
D;D;D;D;D
M_CAP
Benign
0.074
D
MetaRNN
Uncertain
0.51
D;D;D;D;D
MetaSVM
Benign
-0.29
T
MutationAssessor
Uncertain
2.4
M;.;M;.;.
PrimateAI
Pathogenic
0.80
T
PROVEAN
Pathogenic
-5.0
D;.;D;.;.
REVEL
Uncertain
0.38
Sift
Uncertain
0.0020
D;.;T;.;.
Sift4G
Benign
0.073
T;T;D;T;T
Polyphen
1.0
D;.;D;.;.
Vest4
0.88
MutPred
0.39
Gain of methylation at N171 (P = 0.0082);.;Gain of methylation at N171 (P = 0.0082);.;Gain of methylation at N171 (P = 0.0082);
MVP
0.69
MPC
1.1
ClinPred
0.99
D
GERP RS
2.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.79
gMVP
0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-12963362; API