8-54458594-C-G

Variant names:

• chr8-54458594-C-G
• rs12541742
• NM_022454.4:c.307+149C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_022454.4(SOX17):​c.307+149C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000148 in 946,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000088 (0 hom.)
• Consequence: SOX17 NM_022454.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898
• Publications: 6 publications found

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]

SOX17 Gene-Disease associations (from GenCC):

• pulmonary arterial hypertension

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• vesicoureteral reflux 3

  Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• familial vesicoureteral reflux

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BS2: High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX17	NM_022454.4	c.307+149C>G		intron_variant	Intron 1 of 1	ENST00000297316.5	NP_071899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX17	ENST00000297316.5	c.307+149C>G		intron_variant	Intron 1 of 1	1	NM_022454.4	ENSP00000297316.4

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152126 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00136

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000881 AC: 7 AN: 794724 Hom.: 0 AF XY: 0.0000148 AC XY: 6 AN XY: 404182

African (AFR) AF: 0.00 AC: 0 AN: 19052

American (AMR) AF: 0.00 AC: 0 AN: 23964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16994

East Asian (EAS) AF: 0.000218 AC: 7 AN: 32088

South Asian (SAS) AF: 0.00 AC: 0 AN: 55454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2846

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 574560

Other (OTH) AF: 0.00 AC: 0 AN: 37608

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152244 Hom.: 0 Cov.: 33 AF XY: 0.0000806 AC XY: 6 AN XY: 74420

African (AFR) AF: 0.00 AC: 0 AN: 41578

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 1854

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.8
DANN	Benign	0.78
PhyloP100		-0.90

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

Other links and lift over

dbSNP: rs12541742; hg19: chr8-55371154;