rs74999341

Positions:

• chr17-72125313-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000346.4(SOX9):​c.*926T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 227,938 control chromosomes in the GnomAD database, including 326 homozygotes. 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 0.042 (256 hom., cov: 33)
  • Exomes 𝑓: 0.030 (70 hom.)
• Consequence: SOX9 NM_000346.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19

Genes affected

SOX9 (HGNC:11204): (SRY-box transcription factor 9) The protein encoded by this gene recognizes the sequence CCTTGAG along with other members of the HMG-box class DNA-binding proteins. It acts during chondrocyte differentiation and, with steroidogenic factor 1, regulates transcription of the anti-Muellerian hormone (AMH) gene. Deficiencies lead to the skeletal malformation syndrome campomelic dysplasia, frequently with sex reversal. [provided by RefSeq, Jul 2008]

SOX9-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX9	NM_000346.4	c.*926T>C		3_prime_UTR_variant	3/3	ENST00000245479.3	NP_000337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX9	ENST00000245479.3	c.*926T>C		3_prime_UTR_variant	3/3	1	NM_000346.4	ENSP00000245479.2
SOX9-AS1	ENST00000414600.1	n.96+16372A>G		intron_variant		3
ENSG00000288605	ENST00000628742.2	n.147-40268A>G		intron_variant		5
ENSG00000288605	ENST00000674828.1	n.304-79789A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0421 AC: 6403 AN: 152124 Hom.: 253 Cov.: 33

Gnomad AFR AF: 0.0668

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0427

Gnomad EAS AF: 0.0926

Gnomad SAS AF: 0.0190

Gnomad FIN AF: 0.0342

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.0489

GnomAD4 exome AF: 0.0296 AC: 2238 AN: 75696 Hom.: 70 Cov.: 0 AF XY: 0.0282 AC XY: 986 AN XY: 34952

Gnomad4 AFR exome AF: 0.0584

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.0431

Gnomad4 EAS exome AF: 0.0693

Gnomad4 SAS exome AF: 0.00912

Gnomad4 FIN exome AF: 0.0233

Gnomad4 NFE exome AF: 0.0129

Gnomad4 OTH exome AF: 0.0330

GnomAD4 genome AF: 0.0421 AC: 6416 AN: 152242 Hom.: 256 Cov.: 33 AF XY: 0.0448 AC XY: 3336 AN XY: 74430

Gnomad4 AFR AF: 0.0668

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0427

Gnomad4 EAS AF: 0.0930

Gnomad4 SAS AF: 0.0191

Gnomad4 FIN AF: 0.0342

Gnomad4 NFE AF: 0.0117

Gnomad4 OTH AF: 0.0498

Alfa AF: 0.0230 Hom.: 12

Bravo AF: 0.0500

Asia WGS AF: 0.0660 AC: 229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.5
DANN	Benign	0.64

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: rs74999341; hg19: chr17-70121454; COSMIC: COSV55421894; COSMIC: COSV55421894;