17-72121740-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_000346.4(SOX9):​c.349C>G​(p.Gln117Glu) variant causes a missense change. 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

Scores

7
9
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.96
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1
In a helix (size 15) in uniprot entity SOX9_HUMAN there are 7 pathogenic changes around while only 0 benign (100%) in NM_000346.4
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SOX9NM_000346.4 linkuse as main transcriptc.349C>G p.Gln117Glu missense_variant 1/3 ENST00000245479.3 NP_000337.1 P48436

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SOX9ENST00000245479.3 linkuse as main transcriptc.349C>G p.Gln117Glu missense_variant 1/31 NM_000346.4 ENSP00000245479.2 P48436
SOX9-AS1ENST00000414600.1 linkuse as main transcriptn.96+19945G>C intron_variant 3
ENSG00000288605ENST00000628742.2 linkuse as main transcriptn.147-36695G>C intron_variant 5
ENSG00000288605ENST00000674828.1 linkuse as main transcriptn.304-76216G>C 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
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.11
CADD
Pathogenic
31
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.99
D;D
Eigen
Benign
0.015
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.96
.;D
M_CAP
Pathogenic
0.40
D
MetaRNN
Uncertain
0.73
D;D
MetaSVM
Pathogenic
0.82
D
MutationAssessor
Uncertain
2.3
M;M
PrimateAI
Pathogenic
0.80
D
PROVEAN
Uncertain
-2.7
D;.
REVEL
Pathogenic
0.73
Sift
Uncertain
0.0010
D;.
Sift4G
Uncertain
0.0080
D;.
Polyphen
0.099
B;B
Vest4
0.68
MutPred
0.71
Gain of ubiquitination at K122 (P = 0.0444);Gain of ubiquitination at K122 (P = 0.0444);
MVP
0.89
MPC
1.3
ClinPred
0.97
D
GERP RS
4.0
Varity_R
0.96
gMVP
0.99

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: chr17-70117881; API