Variant 17-28364549-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001080837.4(SEBOX):c.292G>A(p.Asp98Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00044 in 1,592,304 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00047 ( 1 hom. )

Consequence

SEBOX
NM_001080837.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.545

Variant links:

Genes affected

SEBOX (HGNC:32942): (SEBOX homeobox) Homeodomain proteins, such as SEBOX, play a key role in coordinating gene expression during development (Cinquanta et al., 2000 [PubMed 10922053]).[supplied by OMIM, Mar 2008]

SEBOX links:

SARM1 (HGNC:17074): (sterile alpha and TIR motif containing 1) Enables NAD+ nucleotidase, cyclic ADP-ribose generating and identical protein binding activity. Involved in NAD catabolic process; positive regulation of neuron death; and response to axon injury. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

SARM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06053433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEBOX	NM_001080837.4 linkuse as main transcript	c.292G>A	p.Asp98Asn	missense_variant	3/3	ENST00000536498.6	NP_001074306.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEBOX	ENST00000536498.6 linkuse as main transcript	c.292G>A	p.Asp98Asn	missense_variant	3/3	5	NM_001080837.4	ENSP00000444503	P1
SARM1	ENST00000379061.8 linkuse as main transcript	n.120+74C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000266

AC:

AN:

232952

Hom.:

AF XY:

0.000302

AC XY:

AN XY:

125826

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000121

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000147

Gnomad NFE exome

AF:

0.000519

Gnomad OTH exome

AF:

0.000180

GnomAD4 exome

AF:

0.000467

AC:

672

AN:

1440198

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

307

AN XY:

713732

show subpopulations

Gnomad4 AFR exome

AF:

0.000121

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000406

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000114

Gnomad4 NFE exome

AF:

0.000579

Gnomad4 OTH exome

AF:

0.000405

GnomAD4 genome

AF:

0.000184

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000274

Hom.:

Bravo

AF:

0.000185

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000481

AC:

ExAC

AF:

0.000331

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 06, 2023

The c.370G>A (p.D124N) alteration is located in exon 3 (coding exon 3) of the SEBOX gene. This alteration results from a G to A substitution at nucleotide position 370, causing the aspartic acid (D) at amino acid position 124 to be replaced by an asparagine (N). 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

0.082

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.63

M_CAP

Benign

0.028

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.48

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.32

REVEL

Benign

0.21

Sift4G

Benign

0.48

Vest4

0.15

MVP

0.048

ClinPred

0.57

GERP RS

3.7

gMVP

0.21

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over