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GeneBe

17-28959444-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_178860.5(SEZ6):c.1800G>A(p.Ser600=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00297 in 1,613,682 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 63 hom., cov: 32)
Exomes 𝑓: 0.0016 ( 65 hom. )

Consequence

SEZ6
NM_178860.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -8.72
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-28959444-C-T is Benign according to our data. Variant chr17-28959444-C-T is described in ClinVar as [Benign]. Clinvar id is 785564.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-8.72 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0551 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEZ6NM_178860.5 linkuse as main transcriptc.1800G>A p.Ser600= synonymous_variant 9/17 ENST00000317338.17
LOC105371716XR_001752822.2 linkuse as main transcriptn.1807+6036C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEZ6ENST00000317338.17 linkuse as main transcriptc.1800G>A p.Ser600= synonymous_variant 9/171 NM_178860.5 A2Q53EL9-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0165
AC:
2508
AN:
152172
Hom.:
63
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0571
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00641
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000265
Gnomad OTH
AF:
0.0100
GnomAD3 exomes
AF:
0.00424
AC:
1054
AN:
248334
Hom.:
24
AF XY:
0.00307
AC XY:
414
AN XY:
134796
show subpopulations
Gnomad AFR exome
AF:
0.0586
Gnomad AMR exome
AF:
0.00275
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000364
Gnomad OTH exome
AF:
0.00166
GnomAD4 exome
AF:
0.00156
AC:
2284
AN:
1461394
Hom.:
65
Cov.:
32
AF XY:
0.00138
AC XY:
1001
AN XY:
727004
show subpopulations
Gnomad4 AFR exome
AF:
0.0537
Gnomad4 AMR exome
AF:
0.00322
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.0000188
Gnomad4 NFE exome
AF:
0.0000971
Gnomad4 OTH exome
AF:
0.00369
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0165
AC:
2509
AN:
152288
Hom.:
63
Cov.:
32
AF XY:
0.0154
AC XY:
1145
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.0570
Gnomad4 AMR
AF:
0.00640
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.000265
Gnomad4 OTH
AF:
0.00994
Alfa
AF:
0.00893
Hom.:
17
Bravo
AF:
0.0188
Asia WGS
AF:
0.00318
AC:
11
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
Cadd
Benign
2.2
Dann
Benign
0.81

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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.

Other links and lift over

dbSNP: rs61737972; hg19: chr17-27286462; API