20-64049125-T-G

Variant names:

• chr20-64049125-T-G
• rs200837124
• NM_018419.3:c.358+34A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018419.3(SOX18):​c.358+34A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (1594 hom., cov: 14)
  • Exomes 𝑓: 0.24 (8721 hom.)
• Consequence: SOX18 NM_018419.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.755
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 20-64049125-T-G is Benign according to our data. Variant chr20-64049125-T-G is described in ClinVar as Benign. ClinVar VariationId is 261030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018419.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX18	NM_018419.3	MANE Select	c.358+34A>C		intron	N/A	NP_060889.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX18	ENST00000340356.9	TSL:1 MANE Select	c.358+34A>C		intron	N/A	ENSP00000341815.7

Frequencies

GnomAD3 genomes AF: 0.303 AC: 20285 AN: 67006 Hom.: 1592 Cov.: 14

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.286

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.284

GnomAD2 exomes AF: 0.205 AC: 15495 AN: 75552 AF XY: 0.213

Gnomad AFR exome AF: 0.207

Gnomad AMR exome AF: 0.198

Gnomad ASJ exome AF: 0.284

Gnomad EAS exome AF: 0.0591

Gnomad FIN exome AF: 0.174

Gnomad NFE exome AF: 0.161

Gnomad OTH exome AF: 0.224

GnomAD4 exome AF: 0.237 AC: 129733 AN: 547650 Hom.: 8721 Cov.: 13 AF XY: 0.237 AC XY: 65825 AN XY: 277312

African (AFR) AF: 0.311 AC: 4109 AN: 13230

American (AMR) AF: 0.132 AC: 2336 AN: 17724

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 2740 AN: 11026

East Asian (EAS) AF: 0.0959 AC: 667 AN: 6954

South Asian (SAS) AF: 0.334 AC: 12016 AN: 35982

European-Finnish (FIN) AF: 0.224 AC: 3061 AN: 13656

Middle Eastern (MID) AF: 0.256 AC: 377 AN: 1470

European-Non Finnish (NFE) AF: 0.232 AC: 98943 AN: 425724

Other (OTH) AF: 0.251 AC: 5484 AN: 21884

GnomAD4 genome AF: 0.303 AC: 20300 AN: 67046 Hom.: 1594 Cov.: 14 AF XY: 0.307 AC XY: 10043 AN XY: 32744

African (AFR) AF: 0.368 AC: 7299 AN: 19832

American (AMR) AF: 0.256 AC: 1609 AN: 6296

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 533 AN: 1730

East Asian (EAS) AF: 0.122 AC: 205 AN: 1678

South Asian (SAS) AF: 0.471 AC: 1320 AN: 2800

European-Finnish (FIN) AF: 0.286 AC: 1149 AN: 4024

Middle Eastern (MID) AF: 0.286 AC: 36 AN: 126

European-Non Finnish (NFE) AF: 0.265 AC: 7725 AN: 29190

Other (OTH) AF: 0.281 AC: 249 AN: 886

Alfa AF: 0.0521 Hom.: 59

Asia WGS AF: 0.171 AC: 513 AN: 3018

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

May 16, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.61
DANN	Benign	0.41
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs200837124; hg19: chr20-62680478;