8-54458059-C-T

Position:

• chr8-54458059-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022454.4(SOX17):​c.-80C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,409,868 control chromosomes in the GnomAD database, including 30,035 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3226 hom., cov: 33)
  • Exomes 𝑓: 0.20 (26809 hom.)
• Consequence: SOX17 NM_022454.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.134

Genes affected

SOX17 (HGNC:18122): (SRY-box transcription factor 17) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 8-54458059-C-T is Benign according to our data. Variant chr8-54458059-C-T is described in ClinVar as [Benign]. Clinvar id is 1293138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX17	NM_022454.4	c.-80C>T		5_prime_UTR_variant	1/2	ENST00000297316.5	NP_071899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX17	ENST00000297316	c.-80C>T		5_prime_UTR_variant	1/2	1	NM_022454.4	ENSP00000297316.4

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28827 AN: 151976 Hom.: 3228 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.175

GnomAD4 exome AF: 0.197 AC: 247915 AN: 1257772 Hom.: 26809 Cov.: 26 AF XY: 0.200 AC XY: 122313 AN XY: 611038

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.349

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.382

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.220

Gnomad4 NFE exome AF: 0.181

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.190 AC: 28834 AN: 152096 Hom.: 3226 Cov.: 33 AF XY: 0.197 AC XY: 14644 AN XY: 74346

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.172

Alfa AF: 0.182 Hom.: 352

Bravo AF: 0.193

Asia WGS AF: 0.348 AC: 1212 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
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: rs62516525; hg19: chr8-55370619;