8-54458912-C-T

Variant names:

• chr8-54458912-C-T
• rs73679444
• NM_022454.4:c.308-146C>T

Variant summary

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

The NM_022454.4(SOX17):​c.308-146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 555,610 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: not found (cov: 34)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SOX17 NM_022454.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 1 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=-0.8).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX17	NM_022454.4	c.308-146C>T		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.308-146C>T		intron_variant	Intron 1 of 1	1	NM_022454.4	ENSP00000297316.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.0000144 AC: 8 AN: 555610 Hom.: 0 AF XY: 0.0000105 AC XY: 3 AN XY: 285626

African (AFR) AF: 0.00 AC: 0 AN: 12212

American (AMR) AF: 0.00 AC: 0 AN: 15396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13466

East Asian (EAS) AF: 0.000289 AC: 8 AN: 27694

South Asian (SAS) AF: 0.00 AC: 0 AN: 43676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29870

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2142

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 382004

Other (OTH) AF: 0.00 AC: 0 AN: 29150

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.74
PhyloP100		-1.4

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: rs73679444; hg19: chr8-55371472;