Variant 18-12986873-C-T details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.03

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]

SEH1L links:

CEP192-DT (HGNC:55313): (CEP192 divergent transcript)

CEP192-DT links:

Genome browser will be placed here

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 linkuse as main transcript	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 linkuse as main transcript	c.1082C>T	p.Thr361Ile	missense_variant	9/9	1	NM_001013437.2	P3	Q96EE3-1
SEH1L	ENST00000262124.15 linkuse as main transcript	c.*1621C>T		3_prime_UTR_variant	9/9	1		A1	Q96EE3-2
SEH1L	ENST00000590843.1 linkuse as main transcript	n.4548C>T		non_coding_transcript_exon_variant	4/4	1
CEP192-DT	ENST00000588211.1 linkuse as main transcript	n.266+1G>A		splice_donor_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

150624

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000133

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000353

AC:

AN:

1417032

Hom.:

Cov.:

AF XY:

0.00000568

AC XY:

AN XY:

704122

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000743

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000184

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000199

AC:

AN:

150624

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73396

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000133

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Benign

-0.033

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.56

M_CAP

Benign

0.035

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.89

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.090

REVEL

Benign

0.080

Sift

Uncertain

0.0080

Sift4G

Benign

0.11

Polyphen

0.0

Vest4

0.23

MutPred

0.26

Loss of phosphorylation at T361 (P = 0.036);

MVP

0.35

MPC

0.32

ClinPred

0.98

GERP RS

4.6

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

gMVP

0.50

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over