chr17-72122794-C-T

Position:

• chr17-72122794-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000346.4(SOX9):​c.507C>T​(p.His169His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,613,870 control chromosomes in the GnomAD database, including 36,273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2607 hom., cov: 32)
  • Exomes 𝑓: 0.21 (33666 hom.)
• Consequence: SOX9 NM_000346.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.441

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 17-72122794-C-T is Benign according to our data. Variant chr17-72122794-C-T is described in ClinVar as [Benign]. Clinvar id is 21164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-72122794-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.441 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX9	NM_000346.4	c.507C>T	p.His169His	synonymous_variant	2/3	ENST00000245479.3	NP_000337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX9	ENST00000245479.3	c.507C>T	p.His169His	synonymous_variant	2/3	1	NM_000346.4	ENSP00000245479.2
SOX9-AS1	ENST00000414600.1	n.96+18891G>A		intron_variant		3
ENSG00000288605	ENST00000628742.2	n.147-37749G>A		intron_variant		5
ENSG00000288605	ENST00000674828.1	n.304-77270G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25240 AN: 152014 Hom.: 2605 Cov.: 32

Gnomad AFR AF: 0.0672

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.0166

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.165

GnomAD3 exomes AF: 0.192 AC: 48228 AN: 251114 Hom.: 5601 AF XY: 0.203 AC XY: 27600 AN XY: 135816

Gnomad AFR exome AF: 0.0618

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.0177

Gnomad SAS exome AF: 0.277

Gnomad FIN exome AF: 0.303

Gnomad NFE exome AF: 0.217

Gnomad OTH exome AF: 0.199

GnomAD4 exome AF: 0.207 AC: 303137 AN: 1461738 Hom.: 33666 Cov.: 36 AF XY: 0.211 AC XY: 153515 AN XY: 727176

Gnomad4 AFR exome AF: 0.0612

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.0187

Gnomad4 SAS exome AF: 0.274

Gnomad4 FIN exome AF: 0.297

Gnomad4 NFE exome AF: 0.213

Gnomad4 OTH exome AF: 0.197

GnomAD4 genome AF: 0.166 AC: 25239 AN: 152132 Hom.: 2607 Cov.: 32 AF XY: 0.170 AC XY: 12643 AN XY: 74366

Gnomad4 AFR AF: 0.0671

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.0169

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.163

Alfa AF: 0.203 Hom.: 2871

Bravo AF: 0.149

Asia WGS AF: 0.130 AC: 451 AN: 3478

EpiCase AF: 0.216

EpiControl AF: 0.213

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 28, 2016	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Camptomelic dysplasia Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

Connective tissue disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

May 17, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	13
DANN	Benign	0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2229989; hg19: chr17-70118935; COSMIC: COSV55423138; COSMIC: COSV55423138;