17-72122941-G-C

Position:

• chr17-72122941-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000346.4(SOX9):​c.654G>C​(p.Met218Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 6.47

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)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23832121).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX9	NM_000346.4	c.654G>C	p.Met218Ile	missense_variant	2/3	ENST00000245479.3	NP_000337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX9	ENST00000245479.3	c.654G>C	p.Met218Ile	missense_variant	2/3	1	NM_000346.4	ENSP00000245479	P1
SOX9-AS1	ENST00000414600.1	n.96+18744C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.50	D;D
Eigen	Benign	0.039
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.84	.;T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.28
Sift	Benign	0.22	T;.
Sift4G	Benign	0.30	T;.
Polyphen		0.0	B;B
Vest4		0.20
MutPred		0.21		Gain of glycosylation at S219 (P = 0.0738);Gain of glycosylation at S219 (P = 0.0738);
MVP		0.65
MPC		0.97
ClinPred		0.93	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.47
gMVP		0.38

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: chr17-70119082;