20-64048039-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018419.3(SOX18):c.*127G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.007 in 1,005,058 control chromosomes in the GnomAD database, including 244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (159 hom., cov: 33)
  • Exomes 𝑓: 0.0038 (85 hom.)
• Consequence: SOX18 NM_018419.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.744

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 20-64048039-C-T is Benign according to our data. Variant chr20-64048039-C-T is described in ClinVar as [Benign]. Clinvar id is 1242190.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX18	NM_018419.3	c.*127G>A		3_prime_UTR_variant	2/2	ENST00000340356.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX18	ENST00000340356.9	c.*127G>A		3_prime_UTR_variant	2/2	1	NM_018419.3	P1

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3793 AN: 152202 Hom.: 158 Cov.: 33

Gnomad AFR AF: 0.0822

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000999

Gnomad OTH AF: 0.0230

GnomAD4 exome AF: 0.00380 AC: 3243 AN: 852738 Hom.: 85 Cov.: 12 AF XY: 0.00342 AC XY: 1496 AN XY: 437846

Gnomad4 AFR exome AF: 0.0849

Gnomad4 AMR exome AF: 0.00916

Gnomad4 ASJ exome AF: 0.00792

Gnomad4 EAS exome AF: 0.0000304

Gnomad4 SAS exome AF: 0.000300

Gnomad4 FIN exome AF: 0.0000304

Gnomad4 NFE exome AF: 0.000975

Gnomad4 OTH exome AF: 0.00888

GnomAD4 genome AF: 0.0249 AC: 3796 AN: 152320 Hom.: 159 Cov.: 33 AF XY: 0.0238 AC XY: 1775 AN XY: 74486

Gnomad4 AFR AF: 0.0821

Gnomad4 AMR AF: 0.0147

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000985

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0116 Hom.: 15

Bravo AF: 0.0282

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	10
Dann	Benign	0.97

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: rs114081080; hg19: chr20-62679392;