rs929651

chr17-72123970-G-Achr17-72123970-G-Cchr17-72123970-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000346.4(SOX9):c.1113G>A(p.Ala371=) 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:6

Conservation

PhyloP100: -2.14

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 196257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-72123970-G-A is described in Lovd as [Benign].

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/exons	MANE	UniProt
SOX9	NM_000346.4 linkuse as main transcript	c.1113G>A	p.Ala371=	synonymous_variant	3/3	ENST00000245479.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX9	ENST00000245479.3 linkuse as main transcript	c.1113G>A	p.Ala371=	synonymous_variant	3/3	1	NM_000346.4	P1
SOX9-AS1	ENST00000414600.1 linkuse as main transcript	n.96+17715C>T		intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes

AF:

0.0310

AC:

5062

AN:

163086

Hom.:

210

AF XY:

0.0264

AC XY:

2428

AN XY:

92062

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 SAS exome

AF:

0.00466

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

Gnomad4 AFR exome

AF:

0.00439

Gnomad4 AMR exome

AF:

0.114

Gnomad4 ASJ exome

AF:

0.0147

Gnomad4 EAS exome

AF:

0.0000929

Gnomad4 SAS exome

AF:

0.00515

Gnomad4 FIN exome

AF:

0.0181

Gnomad4 NFE exome

AF:

0.0254

Gnomad4 OTH exome

AF:

0.0204

GnomAD4 genome

AF:

0.0224

AC:

3386

AN:

151262

Hom.:

Cov.:

AF XY:

0.0227

AC XY:

1681

AN XY:

73930

show subpopulations

Gnomad4 AFR

AF:

0.00694

Gnomad4 AMR

AF:

0.0765

Gnomad4 ASJ

AF:

0.00867

Gnomad4 EAS

AF:

0.00117

Gnomad4 SAS

AF:

0.00771

Gnomad4 FIN

AF:

0.0199

Gnomad4 NFE

AF:

0.0238

Gnomad4 OTH

AF:

0.0215

Alfa

AF:

0.00997

Hom.:

Bravo

AF:

0.0267

Asia WGS

AF:

0.00665

AC:

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 14, 2014	- -

Camptomelic dysplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Connective tissue disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

Cadd

Benign

0.22

Dann

Benign

0.92

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