Variant chr17-28364928-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001080837.4(SEBOX):c.59G>A(p.Arg20Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,612,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

SEBOX
NM_001080837.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.667

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:

ENSG00000273171 (HGNC:):

ENSG00000273171 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=0.07634708).

BP6

Variant 17-28364928-C-T is Benign according to our data. Variant chr17-28364928-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3317006.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEBOX	NM_001080837.4 linkuse as main transcript	c.59G>A	p.Arg20Gln	missense_variant	2/3	ENST00000536498.6	NP_001074306.3	Q9HB31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SEBOX	ENST00000536498.6 linkuse as main transcript	c.59G>A	p.Arg20Gln	missense_variant	2/3	5	NM_001080837.4	ENSP00000444503.3	Q9HB31
ENSG00000273171	ENST00000555059.2 linkuse as main transcript	c.357G>A	p.Pro119Pro	synonymous_variant	3/4	4		ENSP00000452347.3	H0YJW9
SARM1	ENST00000379061.8 linkuse as main transcript	n.121-188C>T		intron_variant		2
ENSG00000258924	ENST00000591482.1 linkuse as main transcript	n.555+4081C>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000731

AC:

AN:

246106

Hom.:

AF XY:

0.0000299

AC XY:

AN XY:

133614

show subpopulations

Gnomad AFR exome

AF:

0.000726

Gnomad AMR exome

AF:

0.000175

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000468

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1460364

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726336

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.000180

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.000138

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.000434

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000280

Hom.:

Bravo

AF:

0.000121

ESP6500AA

AF:

0.000687

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000907

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 04, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

3.9

DANN

Uncertain

0.98

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.77

M_CAP

Benign

0.050

MetaRNN

Benign

0.076

MetaSVM

Uncertain

0.40

PrimateAI

Benign

0.22

REVEL

Uncertain

0.45

Sift4G

Uncertain

0.048

Vest4

0.20

MVP

0.10

ClinPred

0.19

GERP RS

-0.080

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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