8-54458912-C-A

Variant summary

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

The NM_022454.4(SOX17):c.308-146C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 707,512 control chromosomes in the GnomAD database, including 5,391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1246 hom., cov: 34)
  • Exomes 𝑓: 0.11 (4145 hom.)
• Consequence: SOX17 NM_022454.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.35

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 8-54458912-C-A is Benign according to our data. Variant chr8-54458912-C-A is described in ClinVar as [Benign]. Clinvar id is 1222886.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX17	NM_022454.4	c.308-146C>A		intron_variant		ENST00000297316.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX17	ENST00000297316.5	c.308-146C>A		intron_variant		1	NM_022454.4	P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17736 AN: 152074 Hom.: 1238 Cov.: 34

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.0952

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0919

Gnomad OTH AF: 0.110

GnomAD4 exome AF: 0.108 AC: 60004 AN: 555320 Hom.: 4145 AF XY: 0.107 AC XY: 30536 AN XY: 285496

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.165

Gnomad4 ASJ exome AF: 0.0475

Gnomad4 EAS exome AF: 0.318

Gnomad4 SAS exome AF: 0.0927

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.0926

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.117 AC: 17765 AN: 152192 Hom.: 1246 Cov.: 34 AF XY: 0.119 AC XY: 8871 AN XY: 74394

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.0510

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.0947

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.0919

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0991 Hom.: 100

Bravo AF: 0.120

Asia WGS AF: 0.227 AC: 787 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 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.1
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs73679444; hg19: chr8-55371472;