20-64048520-C-G

Variant names:

• chr20-64048520-C-G
• rs183578654
• NM_018419.3:c.801G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_018419.3(SOX18):​c.801G>C​(p.Ala267Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000935 in 1,069,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A267A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.4e-7 (0 hom.)
• Consequence: SOX18 NM_018419.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.415
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=-0.415 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX18	NM_018419.3	c.801G>C	p.Ala267Ala	synonymous_variant	Exon 2 of 2	ENST00000340356.9	NP_060889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX18	ENST00000340356.9	c.801G>C	p.Ala267Ala	synonymous_variant	Exon 2 of 2	1	NM_018419.3	ENSP00000341815.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.35e-7 AC: 1 AN: 1069516 Hom.: 0 Cov.: 31 AF XY: 0.00000198 AC XY: 1 AN XY: 505394

African (AFR) AF: 0.00 AC: 0 AN: 21766

American (AMR) AF: 0.00 AC: 0 AN: 7528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12894

East Asian (EAS) AF: 0.00 AC: 0 AN: 24064

South Asian (SAS) AF: 0.0000465 AC: 1 AN: 21514

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2792

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 915222

Other (OTH) AF: 0.00 AC: 0 AN: 42356

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	9.0
DANN	Benign	0.84
PhyloP100		-0.41

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: rs183578654; hg19: chr20-62679873;