Variant chr20-64048520-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.415

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 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
SOX18	NM_018419.3 linkuse as main transcript	c.801G>A	p.Ala267=	synonymous_variant	2/2	ENST00000340356.9	NP_060889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX18	ENST00000340356.9 linkuse as main transcript	c.801G>A	p.Ala267=	synonymous_variant	2/2	1	NM_018419.3	ENSP00000341815	P1

Frequencies

GnomAD3 genomes

AF:

0.0265

AC:

3992

AN:

150868

Hom.:

163

Cov.:

show subpopulations

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.:

AF XY:

0.00303

AC XY:

1529

AN XY:

505392

show subpopulations

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.:

AF XY:

0.0249

AC XY:

1835

AN XY:

73760

show subpopulations

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.:

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 06, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over