Genetic Variant NM_178860.5:c.2888G>C (chr17-28956223-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_178860.5(SEZ6):c.2888G>C(p.Arg963Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00013 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SEZ6
NM_178860.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.253

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:17804): (pipecolic acid and sarcosine oxidase) Enables L-pipecolate oxidase activity and sarcosine oxidase activity. Involved in L-lysine catabolic process to acetyl-CoA via L-pipecolate. Located in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

PIPOX links:

LOC105371716 (HGNC:):

LOC105371716 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01603651).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEZ6	NM_178860.5 link	c.2888G>C	p.Arg963Pro	missense_variant	Exon 16 of 17	ENST00000317338.17	NP_849191.3	Q53EL9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEZ6	ENST00000317338.17 link	c.2888G>C	p.Arg963Pro	missense_variant	Exon 16 of 17	1	NM_178860.5	ENSP00000312942.11		Q53EL9-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

26258

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000197

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000167

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000671

AC:

AN:

87920

Hom.:

AF XY:

0.000631

AC XY:

AN XY:

50674

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000131

Gnomad ASJ exome

AF:

0.000783

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000731

Gnomad FIN exome

AF:

0.000599

Gnomad NFE exome

AF:

0.00111

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000128

AC:

148

AN:

1153432

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

553650

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000105

Gnomad4 ASJ exome

AF:

0.000275

Gnomad4 EAS exome

AF:

0.000236

Gnomad4 SAS exome

AF:

0.000465

Gnomad4 FIN exome

AF:

0.000859

Gnomad4 NFE exome

AF:

0.0000920

Gnomad4 OTH exome

AF:

0.0000867

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000114

AC:

AN:

26258

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

AN XY:

13290

show subpopulations

Gnomad4 AFR

AF:

0.000197

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000167

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000769

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.046

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.023

.;T;T;.;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.85

D;D;D;D;D

M_CAP

Benign

0.0081

MetaRNN

Benign

0.016

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

M;.;M;.;.

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.98

N;.;.;.;D

REVEL

Benign

0.20

Sift

Benign

0.19

T;.;.;.;D

Sift4G

Benign

0.16

T;T;T;T;T

Polyphen

0.47

P;.;P;.;.

Vest4

0.23

MVP

0.14

MPC

0.38

ClinPred

0.020

GERP RS

-4.3

Varity_R

0.20

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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