17-72123970-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000346.4(SOX9):c.1113G>A(p.Ala371Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0246 in 1,467,744 control chromosomes in the GnomAD database, including 725 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 85 hom., cov: 32)

Exomes 𝑓: 0.025 ( 640 hom. )

Consequence

SOX9
NM_000346.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.14

Publications

5 publications found

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:49321): (SOX9 antisense RNA 1)

SOX9-AS1 links:

ENSG00000288605 (HGNC:):

ENSG00000288605 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 17-72123970-G-A is Benign according to our data. Variant chr17-72123970-G-A is described in ClinVar as Benign. ClinVar VariationId is 196257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX9	NM_000346.4 link	c.1113G>A	p.Ala371Ala	synonymous_variant	Exon 3 of 3	ENST00000245479.3	NP_000337.1	P48436

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX9	ENST00000245479.3 link	c.1113G>A	p.Ala371Ala	synonymous_variant	Exon 3 of 3	1	NM_000346.4	ENSP00000245479.2		P48436

Frequencies

GnomAD3 genomes

AF:

0.0223

AC:

3372

AN:

151152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00696

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0758

Gnomad ASJ

AF:

0.00867

Gnomad EAS

AF:

0.00117

Gnomad SAS

AF:

0.00771

Gnomad FIN

AF:

0.0199

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0238

Gnomad OTH

AF:

0.0217

GnomAD2 exomes

AF:

0.0310

AC:

5062

AN:

163086

AF XY:

0.0264

show subpopulations

Gnomad AFR exome

AF:

0.00459

Gnomad AMR exome

AF:

0.124

Gnomad ASJ exome

AF:

0.0135

Gnomad EAS exome

AF:

0.000302

Gnomad FIN exome

AF:

0.0168

Gnomad NFE exome

AF:

0.0239

Gnomad OTH exome

AF:

0.0214

GnomAD4 exome

AF:

0.0249

AC:

32727

AN:

1316482

Hom.:

640

Cov.:

AF XY:

0.0242

AC XY:

15749

AN XY:

650858

show subpopulations

African (AFR)

AF:

0.00439

AC:

123

AN:

27988

American (AMR)

AF:

0.114

AC:

3648

AN:

31890

Ashkenazi Jewish (ASJ)

AF:

0.0147

AC:

321

AN:

21782

East Asian (EAS)

AF:

0.0000929

AC:

AN:

32308

South Asian (SAS)

AF:

0.00515

AC:

317

AN:

61518

European-Finnish (FIN)

AF:

0.0181

AC:

711

AN:

39250

Middle Eastern (MID)

AF:

0.00486

AC:

AN:

4530

European-Non Finnish (NFE)

AF:

0.0254

AC:

26485

AN:

1043496

Other (OTH)

AF:

0.0204

AC:

1097

AN:

53720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1625

3250

4876

6501

8126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1086

2172

3258

4344

5430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0224

AC:

3386

AN:

151262

Hom.:

Cov.:

AF XY:

0.0227

AC XY:

1681

AN XY:

73930

show subpopulations

African (AFR)

AF:

0.00694

AC:

287

AN:

41382

American (AMR)

AF:

0.0765

AC:

1163

AN:

15196

Ashkenazi Jewish (ASJ)

AF:

0.00867

AC:

AN:

3462

East Asian (EAS)

AF:

0.00117

AC:

AN:

5130

South Asian (SAS)

AF:

0.00771

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.0199

AC:

205

AN:

10296

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0238

AC:

1610

AN:

67702

Other (OTH)

AF:

0.0215

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

163

325

488

650

813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00997

Hom.:

Bravo

AF:

0.0267

Asia WGS

AF:

0.00665

AC:

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Nov 14, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

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

- -

not provided

Benign:2

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:1

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

Jul 22, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.22

(source)

DANN

Benign

0.92

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over