Variant chr18-12984145-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000399892.7(SEH1L):c.1025C>A(p.Thr342Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,612,740 control chromosomes in the GnomAD database, including 340,975 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.72 ( 40939 hom., cov: 34)

Exomes 𝑓: 0.64 ( 300036 hom. )

Consequence

SEH1L
ENST00000399892.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.37

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.810506E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEH1L	NM_001013437.2 linkuse as main transcript	c.1025C>A	p.Thr342Asn	missense_variant	8/9	ENST00000399892.7	NP_001013455.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEH1L	ENST00000399892.7 linkuse as main transcript	c.1025C>A	p.Thr342Asn	missense_variant	8/9	1	NM_001013437.2	ENSP00000382779	P3	Q96EE3-1
SEH1L	ENST00000262124.15 linkuse as main transcript	c.1025C>A	p.Thr342Asn	missense_variant	8/9	1		ENSP00000262124	A1	Q96EE3-2
SEH1L	ENST00000590843.1 linkuse as main transcript	n.2869C>A		non_coding_transcript_exon_variant	3/4	1
SEH1L	ENST00000592582.5 linkuse as main transcript	n.3548C>A		non_coding_transcript_exon_variant	5/6	1

Frequencies

GnomAD3 genomes

AF:

0.719

AC:

109436

AN:

152108

Hom.:

40877

Cov.:

show subpopulations

Gnomad AFR

AF:

0.928

Gnomad AMI

AF:

0.643

Gnomad AMR

AF:

0.681

Gnomad ASJ

AF:

0.752

Gnomad EAS

AF:

0.805

Gnomad SAS

AF:

0.730

Gnomad FIN

AF:

0.612

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.609

Gnomad OTH

AF:

0.724

GnomAD3 exomes

AF:

0.671

AC:

168518

AN:

251240

Hom.:

57664

AF XY:

0.670

AC XY:

90938

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.936

Gnomad AMR exome

AF:

0.617

Gnomad ASJ exome

AF:

0.766

Gnomad EAS exome

AF:

0.786

Gnomad SAS exome

AF:

0.719

Gnomad FIN exome

AF:

0.612

Gnomad NFE exome

AF:

0.622

Gnomad OTH exome

AF:

0.649

GnomAD4 exome

AF:

0.636

AC:

929302

AN:

1460514

Hom.:

300036

Cov.:

AF XY:

0.638

AC XY:

463843

AN XY:

726614

show subpopulations

Gnomad4 AFR exome

AF:

0.944

Gnomad4 AMR exome

AF:

0.622

Gnomad4 ASJ exome

AF:

0.757

Gnomad4 EAS exome

AF:

0.838

Gnomad4 SAS exome

AF:

0.720

Gnomad4 FIN exome

AF:

0.604

Gnomad4 NFE exome

AF:

0.610

Gnomad4 OTH exome

AF:

0.672

GnomAD4 genome

AF:

0.720

AC:

109553

AN:

152226

Hom.:

40939

Cov.:

AF XY:

0.720

AC XY:

53601

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.928

Gnomad4 AMR

AF:

0.681

Gnomad4 ASJ

AF:

0.752

Gnomad4 EAS

AF:

0.805

Gnomad4 SAS

AF:

0.730

Gnomad4 FIN

AF:

0.612

Gnomad4 NFE

AF:

0.609

Gnomad4 OTH

AF:

0.728

Alfa

AF:

0.646

Hom.:

65034

Bravo

AF:

0.735

TwinsUK

AF:

0.610

AC:

2261

ALSPAC

AF:

0.609

AC:

2347

ESP6500AA

AF:

0.921

AC:

4059

ESP6500EA

AF:

0.621

AC:

5337

ExAC

AF:

0.677

AC:

82181

Asia WGS

AF:

0.815

AC:

2832

AN:

3478

EpiCase

AF:

0.634

EpiControl

AF:

0.644

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.32

DEOGEN2

Benign

0.041

T;.

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.077

T;T

MetaRNN

Benign

5.8e-7

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.6

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.44

PROVEAN

Benign

0.87

N;N

REVEL

Benign

0.10

Sift

Benign

0.80

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.0

B;B

Vest4

0.060

MPC

0.34

ClinPred

0.0021

GERP RS

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.024

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over