Variant rs1976165 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_178860.5(SEZ6):c.1636A>G(p.Thr546Ala) variant causes a missense change. The variant allele was found at a frequency of 0.27 in 1,613,136 control chromosomes in the GnomAD database, including 61,549 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.32 ( 8366 hom., cov: 32)

Exomes 𝑓: 0.27 ( 53183 hom. )

Consequence

SEZ6
NM_178860.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.86

Variant links:

Genes affected

SEZ6 (HGNC:15955): (seizure related 6 homolog) The protein encoded by this gene is thought to contain five cysteine-rich motifs that are similar to sushi domains, as well as two domains similar to the amino terminal half of the CUB (for complement C1r/C1s, Uegf, Bmp1) domain. Mutations in this gene have been associated with febrile seizures. [provided by RefSeq, Jul 2016]

SEZ6 links:

PIPOX (HGNC:):

PIPOX links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002216816).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEZ6	NM_178860.5 linkuse as main transcript	c.1636A>G	p.Thr546Ala	missense_variant	8/17	ENST00000317338.17	NP_849191.3	Q53EL9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEZ6	ENST00000317338.17 linkuse as main transcript	c.1636A>G	p.Thr546Ala	missense_variant	8/17	1	NM_178860.5	ENSP00000312942.11		Q53EL9-1

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48194

AN:

151970

Hom.:

8360

Cov.:

show subpopulations

Gnomad AFR

AF:

0.460

Gnomad AMI

AF:

0.225

Gnomad AMR

AF:

0.300

Gnomad ASJ

AF:

0.277

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.366

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.327

GnomAD3 exomes

AF:

0.283

AC:

70036

AN:

247794

Hom.:

10464

AF XY:

0.284

AC XY:

38144

AN XY:

134464

show subpopulations

Gnomad AFR exome

AF:

0.465

Gnomad AMR exome

AF:

0.259

Gnomad ASJ exome

AF:

0.271

Gnomad EAS exome

AF:

0.240

Gnomad SAS exome

AF:

0.374

Gnomad FIN exome

AF:

0.267

Gnomad NFE exome

AF:

0.251

Gnomad OTH exome

AF:

0.279

GnomAD4 exome

AF:

0.265

AC:

387339

AN:

1461046

Hom.:

53183

Cov.:

AF XY:

0.267

AC XY:

194316

AN XY:

726752

show subpopulations

Gnomad4 AFR exome

AF:

0.469

Gnomad4 AMR exome

AF:

0.268

Gnomad4 ASJ exome

AF:

0.270

Gnomad4 EAS exome

AF:

0.248

Gnomad4 SAS exome

AF:

0.363

Gnomad4 FIN exome

AF:

0.264

Gnomad4 NFE exome

AF:

0.250

Gnomad4 OTH exome

AF:

0.288

GnomAD4 genome

AF:

0.317

AC:

48231

AN:

152090

Hom.:

8366

Cov.:

AF XY:

0.317

AC XY:

23575

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.460

Gnomad4 AMR

AF:

0.300

Gnomad4 ASJ

AF:

0.277

Gnomad4 EAS

AF:

0.239

Gnomad4 SAS

AF:

0.364

Gnomad4 FIN

AF:

0.266

Gnomad4 NFE

AF:

0.248

Gnomad4 OTH

AF:

0.324

Alfa

AF:

0.266

Hom.:

13592

Bravo

AF:

0.326

TwinsUK

AF:

0.248

AC:

920

ALSPAC

AF:

0.253

AC:

975

ESP6500AA

AF:

0.429

AC:

1790

ESP6500EA

AF:

0.255

AC:

2162

ExAC

AF:

0.287

AC:

34741

Asia WGS

AF:

0.339

AC:

1182

AN:

3478

EpiCase

AF:

0.254

EpiControl

AF:

0.262

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0091

.;T;T;.;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.44

T;T;T;T;T

MetaRNN

Benign

0.0022

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.73

N;.;N;.;.

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.26

N;.;.;.;N

REVEL

Benign

0.079

Sift

Benign

0.31

T;.;.;.;T

Sift4G

Benign

0.19

T;T;T;T;T

Polyphen

0.0

B;.;B;.;.

Vest4

0.033

MPC

0.26

ClinPred

0.0076

GERP RS

5.1

Varity_R

0.067

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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