Genetic Variant SOX18:p.Glu238Gln (chr20-64048609-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018419.3(SOX18):c.712G>C(p.Glu238Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,100,096 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

SOX18
NM_018419.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.69

Publications

1 publications found

Variant links:

Genes affected

SOX18 (HGNC:11194): (SRY-box transcription factor 18) This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins. This protein plays a role in hair, blood vessel, and lymphatic vessel development. Mutations in this gene have been associated with recessive and dominant forms of hypotrichosis-lymphedema-telangiectasia. [provided by RefSeq, Jul 2008]

SOX18 Gene-Disease associations (from GenCC):

hypotrichosis-lymphedema-telangiectasia-renal defect syndrome
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
hypotrichosis-lymphedema-telangiectasia syndrome
Inheritance: AR, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
hypotrichosis-lymphedema-telangiectasia syndrome (grouping)
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SOX18 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX18	NM_018419.3 link	c.712G>C	p.Glu238Gln	missense_variant	Exon 2 of 2	ENST00000340356.9	NP_060889.1	P35713

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX18	ENST00000340356.9 link	c.712G>C	p.Glu238Gln	missense_variant	Exon 2 of 2	1	NM_018419.3	ENSP00000341815.7		P35713

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000182

AC:

AN:

1100096

Hom.:

Cov.:

AF XY:

0.00000191

AC XY:

AN XY:

522302

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22364

American (AMR)

AF:

0.00

AC:

AN:

7946

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13974

East Asian (EAS)

AF:

0.00

AC:

AN:

25128

South Asian (SAS)

AF:

0.00

AC:

AN:

27340

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22780

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2950

European-Non Finnish (NFE)

AF:

0.00000214

AC:

AN:

933416

Other (OTH)

AF:

0.00

AC:

AN:

44198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.024

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.54

M_CAP

Pathogenic

0.91

MetaRNN

Uncertain

0.46

MetaSVM

Uncertain

0.28

MutationAssessor

Uncertain

2.7

PhyloP100

6.7

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.34

Sift

Uncertain

0.020

Sift4G

Benign

0.14

Polyphen

0.98

Vest4

0.20

MutPred

0.20

Loss of glycosylation at P237 (P = 0.208);

MVP

0.63

ClinPred

0.96

GERP RS

3.8

Varity_R

0.31

gMVP

0.41

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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