dbSNP rs9910163: SEBOX:p.Leu181Trp (chr17-28364299-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080837.4(SEBOX):c.542T>G(p.Leu181Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/18 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SEBOX
NM_001080837.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0940

Publications

26 publications found

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:

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12380049).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEBOX	NM_001080837.4 link	c.542T>G	p.Leu181Trp	missense_variant	Exon 3 of 3	ENST00000536498.6	NP_001074306.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SEBOX	ENST00000536498.6 link	c.542T>G	p.Leu181Trp	missense_variant	Exon 3 of 3	5	NM_001080837.4	ENSP00000444503.3
ENSG00000273171	ENST00000555059.2 link	c.*393T>G		3_prime_UTR_variant	Exon 4 of 4	4		ENSP00000452347.3
ENSG00000258924	ENST00000591482.1 link	n.555+3452A>C		intron_variant	Intron 5 of 5	2
SARM1	ENST00000379061.8 link	n.-57A>C		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000425

AC:

AN:

235462

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000941

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000138

AC:

AN:

1453134

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721874

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33368

American (AMR)

AF:

0.00

AC:

AN:

43286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25978

East Asian (EAS)

AF:

0.00

AC:

AN:

39356

South Asian (SAS)

AF:

0.00

AC:

AN:

84594

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52846

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1107852

Other (OTH)

AF:

0.00

AC:

AN:

60100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

144430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.91

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.28

M_CAP

Benign

0.029

MetaRNN

Benign

0.12

MetaSVM

Uncertain

0.13

PhyloP100

0.094

PrimateAI

Benign

0.38

REVEL

Uncertain

0.37

Sift4G

Uncertain

0.012

Vest4

0.28

ClinPred

0.099

GERP RS

2.1

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over