17-72121309-G-A

Position:

• chr17-72121309-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000245479(SOX9):​c.-83G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00319 in 1,285,480 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (46 hom., cov: 31)
  • Exomes 𝑓: 0.0017 (39 hom.)
• Consequence: SOX9 ENST00000245479 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.225

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 17-72121309-G-A is Benign according to our data. Variant chr17-72121309-G-A is described in ClinVar as [Benign]. Clinvar id is 1290975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.014 (2129/152200) while in subpopulation AFR AF= 0.0475 (1972/41550). AF 95% confidence interval is 0.0457. There are 46 homozygotes in gnomad4. There are 1021 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2129 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX9	NM_000346.4	c.-83G>A		5_prime_UTR_variant	1/3	ENST00000245479.3	NP_000337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX9	ENST00000245479	c.-83G>A		5_prime_UTR_variant	1/3	1	NM_000346.4	ENSP00000245479.2
SOX9-AS1	ENST00000414600.1	n.96+20376C>T		intron_variant		3
ENSG00000288605	ENST00000628742.2	n.147-36264C>T		intron_variant		5
ENSG00000288605	ENST00000674828.1	n.304-75785C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2123 AN: 152084 Hom.: 46 Cov.: 31

Gnomad AFR AF: 0.0474

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00661

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.00174 AC: 1974 AN: 1133280 Hom.: 39 Cov.: 16 AF XY: 0.00157 AC XY: 904 AN XY: 574914

Gnomad4 AFR exome AF: 0.0503

Gnomad4 AMR exome AF: 0.00402

Gnomad4 ASJ exome AF: 0.00333

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000167

Gnomad4 OTH exome AF: 0.00431

GnomAD4 genome AF: 0.0140 AC: 2129 AN: 152200 Hom.: 46 Cov.: 31 AF XY: 0.0137 AC XY: 1021 AN XY: 74394

Gnomad4 AFR AF: 0.0475

Gnomad4 AMR AF: 0.00660

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0000537 Hom.: 0

Bravo AF: 0.0162

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	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
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: rs116826102; hg19: chr17-70117450;