17-72122794-C-T

Position:

chr17-72122794-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.441

Variant links:

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 links:

SOX9-AS1 (HGNC:):

SOX9-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.507C>T	p.His169His	synonymous_variant	2/3	ENST00000245479.3	NP_000337.1	P48436

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SOX9	ENST00000245479.3 linkuse as main transcript	c.507C>T	p.His169His	synonymous_variant	2/3	1	NM_000346.4	ENSP00000245479.2	P48436
SOX9-AS1	ENST00000414600.1 linkuse as main transcript	n.96+18891G>A		intron_variant		3
ENSG00000288605	ENST00000628742.2 linkuse as main transcript	n.147-37749G>A		intron_variant		5
ENSG00000288605	ENST00000674828.1 linkuse as main transcript	n.304-77270G>A		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25240

AN:

152014

Hom.:

2605

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.211

AC XY:

153515

AN XY:

727176

show subpopulations

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.:

AF XY:

0.170

AC XY:

12643

AN XY:

74366

show subpopulations

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

LINK: link

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over