17-72121433-G-C

Position:

• chr17-72121433-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000346.4(SOX9):​c.42G>C​(p.Gln14His) 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: 31)
• Consequence: SOX9 NM_000346.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX9	NM_000346.4	c.42G>C	p.Gln14His	missense_variant	1/3	ENST00000245479.3	NP_000337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX9	ENST00000245479.3	c.42G>C	p.Gln14His	missense_variant	1/3	1	NM_000346.4	ENSP00000245479.2
SOX9-AS1	ENST00000414600.1	n.96+20252C>G		intron_variant		3
ENSG00000288605	ENST00000628742.2	n.147-36388C>G		intron_variant		5
ENSG00000288605	ENST00000674828.1	n.304-75909C>G		intron_variant

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.93	.;D
M_CAP	Pathogenic	0.83	D
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Pathogenic	0.94	D
MutationAssessor	Benign	1.5	L;L
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.5	N;.
REVEL	Uncertain	0.56
Sift	Benign	0.25	T;.
Sift4G	Benign	0.18	T;.
Polyphen		0.99	D;D
Vest4		0.32
MutPred		0.046		Loss of methylation at K16 (P = 0.1172);Loss of methylation at K16 (P = 0.1172);
MVP		0.95
MPC		1.9
ClinPred		0.85	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.22
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-70117574;