rs575451633

Variant names:

• chr17-72121467-A-C
• NM_000346.4:c.76A>C

Your query was ambiguous. Multiple possible variants found:

• chr17-72121467-A-C
• chr17-72121467-A-G
• chr17-72121467-A-T

Variant summary

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

The NM_000346.4(SOX9):​c.76A>C​(p.Met26Leu) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M26V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SOX9 NM_000346.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.01

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

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=0.17864013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX9	NM_000346.4	c.76A>C	p.Met26Leu	missense_variant	Exon 1 of 3	ENST00000245479.3	NP_000337.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX9	ENST00000245479.3	c.76A>C	p.Met26Leu	missense_variant	Exon 1 of 3	1	NM_000346.4	ENSP00000245479.2
SOX9-AS1	ENST00000414600.1	n.96+20218T>G		intron_variant	Intron 1 of 1	3
ENSG00000288605	ENST00000628742.2	n.147-36422T>G		intron_variant	Intron 2 of 6	5
ENSG00000288605	ENST00000674828.1	n.304-75943T>G		intron_variant	Intron 1 of 3

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	0.10
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Benign	0.93
DEOGEN2	Uncertain	0.68	D;D
Eigen	Benign	-0.13
Eigen_PC	Benign	0.019
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.92	.;D
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	2.0	M;M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.2	N;.
REVEL	Uncertain	0.33
Sift	Benign	0.14	T;.
Sift4G	Benign	0.29	T;.
Polyphen		0.0	B;B
Vest4		0.25
MutPred		0.20		Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);
MVP		0.84
MPC		0.82
ClinPred		0.75	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.36
gMVP		0.37

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: chr17-70117608;