chr17-72123970-G-A

Position:

• chr17-72123970-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -2.14

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 -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	Protein	UniProt
SOX9	NM_000346.4	c.1113G>A	p.Ala371Ala	synonymous_variant	3/3	ENST00000245479.3	NP_000337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX9	ENST00000245479.3	c.1113G>A	p.Ala371Ala	synonymous_variant	3/3	1	NM_000346.4	ENSP00000245479.2
SOX9-AS1	ENST00000414600.1	n.96+17715C>T		intron_variant		3
ENSG00000288605	ENST00000628742.2	n.147-38925C>T		intron_variant		5
ENSG00000288605	ENST00000674828.1	n.304-78446C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3372 AN: 151152 Hom.: 81 Cov.: 32

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

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.: 37 AF XY: 0.0242 AC XY: 15749 AN XY: 650858

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.: 85 Cov.: 32 AF XY: 0.0227 AC XY: 1681 AN XY: 73930

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.: 15

Bravo AF: 0.0267

Asia WGS AF: 0.00665 AC: 24 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

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

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Camptomelic dysplasia Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

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

Other links and lift over

dbSNP: rs929651; hg19: chr17-70120111;