Genetic Variant SEH1L:p.Ala195Ala (chr18-12971216-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001013437.2(SEH1L):c.585C>T(p.Ala195Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00537 in 1,613,602 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0040 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 37 hom. )

Consequence

SEH1L
NM_001013437.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.14

Publications

4 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 18-12971216-C-T is Benign according to our data. Variant chr18-12971216-C-T is described in ClinVar as Benign. ClinVar VariationId is 710782.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.13 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013437.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEH1L	NM_001013437.2	MANE Select	c.585C>T	p.Ala195Ala	synonymous	Exon 5 of 9	NP_001013455.1	Q96EE3-1
	SEH1L	NM_031216.4		c.585C>T	p.Ala195Ala	synonymous	Exon 5 of 9	NP_112493.2	Q96EE3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEH1L	ENST00000399892.7	TSL:1 MANE Select	c.585C>T	p.Ala195Ala	synonymous	Exon 5 of 9	ENSP00000382779.1	Q96EE3-1
SEH1L	ENST00000262124.15	TSL:1	c.585C>T	p.Ala195Ala	synonymous	Exon 5 of 9	ENSP00000262124.10	Q96EE3-2
SEH1L	ENST00000962384.1		c.681C>T	p.Ala227Ala	synonymous	Exon 6 of 10	ENSP00000632443.1

Frequencies

GnomAD3 genomes

AF:

0.00403

AC:

613

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00840

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00666

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00441

AC:

1110

AN:

251450

AF XY:

0.00447

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00859

Gnomad NFE exome

AF:

0.00714

Gnomad OTH exome

AF:

0.00440

GnomAD4 exome

AF:

0.00551

AC:

8048

AN:

1461362

Hom.:

Cov.:

AF XY:

0.00537

AC XY:

3902

AN XY:

727020

show subpopulations

African (AFR)

AF:

0.000717

AC:

AN:

33462

American (AMR)

AF:

0.00119

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00245

AC:

AN:

26130

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39690

South Asian (SAS)

AF:

0.000591

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00888

AC:

474

AN:

53408

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00643

AC:

7147

AN:

1111554

Other (OTH)

AF:

0.00379

AC:

229

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

366

732

1099

1465

1831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

262

524

786

1048

1310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00403

AC:

613

AN:

152240

Hom.:

Cov.:

AF XY:

0.00376

AC XY:

280

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

41532

American (AMR)

AF:

0.000719

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.000830

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00840

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00666

AC:

453

AN:

68014

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

110

138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00561

Hom.:

Bravo

AF:

0.00327

EpiCase

AF:

0.00551

EpiControl

AF:

0.00551

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over