rs183578654

chr20-64048520-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_018419.3(SOX18):c.801G>A(p.Ala267=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00603 in 1,220,490 control chromosomes in the GnomAD database, including 272 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (164 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (108 hom.)
• Consequence: SOX18 NM_018419.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.415

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]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 20-64048520-C-T is Benign according to our data. Variant chr20-64048520-C-T is described in ClinVar as [Benign]. Clinvar id is 261031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-64048520-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.415 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX18	NM_018419.3	c.801G>A	p.Ala267=	synonymous_variant	2/2	ENST00000340356.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX18	ENST00000340356.9	c.801G>A	p.Ala267=	synonymous_variant	2/2	1	NM_018419.3	P1

Frequencies

GnomAD3 genomes AF: 0.0265 AC: 3992 AN: 150868 Hom.: 163 Cov.: 33

Gnomad AFR AF: 0.0874

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0152

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0256

Gnomad NFE AF: 0.000976

Gnomad OTH AF: 0.0236

GnomAD4 exome AF: 0.00314 AC: 3363 AN: 1069514 Hom.: 108 Cov.: 31 AF XY: 0.00303 AC XY: 1529 AN XY: 505392

Gnomad4 AFR exome AF: 0.0907

Gnomad4 AMR exome AF: 0.0105

Gnomad4 ASJ exome AF: 0.00783

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.0000468

Gnomad4 NFE exome AF: 0.000933

Gnomad4 OTH exome AF: 0.00763

GnomAD4 genome AF: 0.0264 AC: 3993 AN: 150976 Hom.: 164 Cov.: 33 AF XY: 0.0249 AC XY: 1835 AN XY: 73760

Gnomad4 AFR AF: 0.0873

Gnomad4 AMR AF: 0.0150

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000962

Gnomad4 OTH AF: 0.0234

Alfa AF: 0.0169 Hom.: 18

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 06, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 11, 2023	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
Cadd	Benign	9.7
Dann	Benign	0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs183578654; hg19: chr20-62679873;