dbSNP rs1278754693: SEH1L:p.Gly261Val (chr18-12982538-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001013437.2(SEH1L):c.782G>T(p.Gly261Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SEH1L
NM_001013437.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.01

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26138633).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEH1L	NM_001013437.2 link	c.782G>T	p.Gly261Val	missense_variant	Exon 7 of 9	ENST00000399892.7	NP_001013455.1	Q96EE3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEH1L	ENST00000399892.7 link	c.782G>T	p.Gly261Val	missense_variant	Exon 7 of 9	1	NM_001013437.2	ENSP00000382779.1		Q96EE3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000404

AC:

AN:

247370

AF XY:

0.00000749

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000298

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458540

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725376

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33332

American (AMR)

AF:

0.0000228

AC:

AN:

43904

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26036

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.00

AC:

AN:

85072

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111096

Other (OTH)

AF:

0.00

AC:

AN:

60286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 16, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.782G>T (p.G261V) alteration is located in exon 7 (coding exon 7) of the SEH1L gene. This alteration results from a G to T substitution at nucleotide position 782, causing the glycine (G) at amino acid position 261 to be replaced by a valine (V). 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

Benign

0.092

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

T;.

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.035

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-0.60

MutationAssessor

Benign

2.0

M;M

PhyloP100

5.0

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.3

D;D

REVEL

Uncertain

0.29

Sift

Uncertain

0.020

D;D

Sift4G

Benign

0.19

T;T

Polyphen

0.26

B;P

Vest4

0.52

MutPred

0.40

Loss of disorder (P = 0.0264);Loss of disorder (P = 0.0264);

MVP

0.56

MPC

0.51

ClinPred

0.58

GERP RS

5.9

Varity_R

0.37

gMVP

0.44

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over