NM_018419.3:c.243C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018419.3(SOX18):c.243C>T(p.Asp81Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00319 in 1,511,390 control chromosomes in the GnomAD database, including 137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 86 hom., cov: 31)

Exomes 𝑓: 0.0016 ( 51 hom. )

Consequence

SOX18
NM_018419.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.167

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: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 20-64049274-G-A is Benign according to our data. Variant chr20-64049274-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 261029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.167 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX18	NM_018419.3 link	c.243C>T	p.Asp81Asp	synonymous_variant	Exon 1 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.243C>T	p.Asp81Asp	synonymous_variant	Exon 1 of 2	1	NM_018419.3	ENSP00000341815.7		P35713

Frequencies

GnomAD3 genomes

AF:

0.0179

AC:

2678

AN:

149976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0621

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00550

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000209

Gnomad OTH

AF:

0.0107

GnomAD2 exomes

AF:

0.00373

AC:

765

AN:

205302

AF XY:

0.00280

show subpopulations

Gnomad AFR exome

AF:

0.0627

Gnomad AMR exome

AF:

0.00273

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000143

Gnomad OTH exome

AF:

0.00125

GnomAD4 exome

AF:

0.00156

AC:

2128

AN:

1361310

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

898

AN XY:

677114

show subpopulations

African (AFR)

AF:

0.0623

AC:

1710

AN:

27456

American (AMR)

AF:

0.00310

AC:

116

AN:

37390

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22312

East Asian (EAS)

AF:

0.00

AC:

AN:

29584

South Asian (SAS)

AF:

0.000136

AC:

AN:

81010

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48618

Middle Eastern (MID)

AF:

0.00102

AC:

AN:

4900

European-Non Finnish (NFE)

AF:

0.0000938

AC:

AN:

1055780

Other (OTH)

AF:

0.00345

AC:

187

AN:

54260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

119

239

358

478

597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

192

256

320

<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

AF:

0.0179

AC:

2688

AN:

150080

Hom.:

Cov.:

AF XY:

0.0175

AC XY:

1282

AN XY:

73258

show subpopulations

African (AFR)

AF:

0.0622

AC:

2568

AN:

41304

American (AMR)

AF:

0.00549

AC:

AN:

15112

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3424

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9856

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000209

AC:

AN:

67120

Other (OTH)

AF:

0.0106

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

128

256

385

513

641

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00572

Hom.:

Bravo

AF:

0.0208

Asia WGS

AF:

0.00320

AC:

AN:

3138

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 06, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 18, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hypotrichosis-lymphedema-telangiectasia syndrome;C4317151:Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome

Benign:1

Aug 12, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

0.17

PromoterAI

0.057

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over