17-72122794-C-T

Variant names:

• chr17-72122794-C-T
• rs2229989
• NM_000346.4:c.507C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 37 publications found

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:49321): (SOX9 antisense RNA 1)

ENSG00000288605 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 21164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000346.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX9	NM_000346.4	MANE Select	c.507C>T	p.His169His	synonymous	Exon 2 of 3	NP_000337.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX9	ENST00000245479.3	TSL:1 MANE Select	c.507C>T	p.His169His	synonymous	Exon 2 of 3	ENSP00000245479.2
	SOX9-AS1	ENST00000414600.1	TSL:3	n.96+18891G>A		intron	N/A
	ENSG00000288605	ENST00000628742.2	TSL:5	n.147-37749G>A		intron	N/A

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

GnomAD2 exomes AF: 0.192 AC: 48228 AN: 251114 AF XY: 0.203

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 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

African (AFR) AF: 0.0612 AC: 2048 AN: 33480

American (AMR) AF: 0.113 AC: 5069 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 5939 AN: 26136

East Asian (EAS) AF: 0.0187 AC: 741 AN: 39700

South Asian (SAS) AF: 0.274 AC: 23594 AN: 86256

European-Finnish (FIN) AF: 0.297 AC: 15863 AN: 53396

Middle Eastern (MID) AF: 0.181 AC: 1042 AN: 5768

European-Non Finnish (NFE) AF: 0.213 AC: 236935 AN: 1111888

Other (OTH) AF: 0.197 AC: 11906 AN: 60392

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

African (AFR) AF: 0.0671 AC: 2785 AN: 41534

American (AMR) AF: 0.138 AC: 2116 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 759 AN: 3470

East Asian (EAS) AF: 0.0169 AC: 87 AN: 5162

South Asian (SAS) AF: 0.268 AC: 1294 AN: 4824

European-Finnish (FIN) AF: 0.296 AC: 3133 AN: 10578

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14488 AN: 67972

Other (OTH) AF: 0.163 AC: 343 AN: 2106

Alfa AF: 0.193 Hom.: 3843

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

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Jun 28, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:3

Nov 25, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Camptomelic dysplasia Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Connective tissue disorder Benign:1

May 17, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	13
DANN	Benign	0.96
PhyloP100		0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=92/8	polymorphism (auto)

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