17-72124037-C-G

Variant names:

• chr17-72124037-C-G
• rs1057518216
• NM_000346.4:c.1180C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000346.4(SOX9):​c.1180C>G​(p.Arg394Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SOX9 NM_000346.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX9	NM_000346.4	MANE Select	c.1180C>G	p.Arg394Gly	missense	Exon 3 of 3	NP_000337.1	P48436

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX9	ENST00000245479.3	TSL:1 MANE Select	c.1180C>G	p.Arg394Gly	missense	Exon 3 of 3	ENSP00000245479.2	P48436
	SOX9	ENST00000877559.1		c.1345C>G	p.Arg449Gly	missense	Exon 3 of 3	ENSP00000547618.1
	SOX9-AS1	ENST00000414600.1	TSL:3	n.96+17648G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.90	D
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.077
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.63	T
M_CAP	Pathogenic	0.30	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	0.33	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		-0.13
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.028	D
Polyphen		0.99	D
Vest4		0.82
MutPred		0.24		Loss of catalytic residue at R394 (P = 0.0024)
MVP		0.70
MPC		1.4
ClinPred		0.97	D
GERP RS		0.12
Varity_R		0.43
gMVP		0.61
Mutation Taster		=16/84	disease causing

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: rs1057518216; hg19: chr17-70120178;