rs74999341

Variant names:

• chr17-72125313-T-C
• rs74999341
• NM_000346.4:c.*926T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000346.4(SOX9):​c.*926T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 227,938 control chromosomes in the GnomAD database, including 326 homozygotes. 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: 𝑓 0.042 (256 hom., cov: 33)
  • Exomes 𝑓: 0.030 (70 hom.)
• Consequence: SOX9 NM_000346.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0992 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX9	NM_000346.4	MANE Select	c.*926T>C		3_prime_UTR	Exon 3 of 3	NP_000337.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX9	ENST00000245479.3	TSL:1 MANE Select	c.*926T>C		3_prime_UTR	Exon 3 of 3	ENSP00000245479.2
	SOX9-AS1	ENST00000414600.1	TSL:3	n.96+16372A>G		intron	N/A
	ENSG00000288605	ENST00000628742.2	TSL:5	n.147-40268A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0421 AC: 6403 AN: 152124 Hom.: 253 Cov.: 33

Gnomad AFR AF: 0.0668

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0427

Gnomad EAS AF: 0.0926

Gnomad SAS AF: 0.0190

Gnomad FIN AF: 0.0342

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.0489

GnomAD4 exome AF: 0.0296 AC: 2238 AN: 75696 Hom.: 70 Cov.: 0 AF XY: 0.0282 AC XY: 986 AN XY: 34952

African (AFR) AF: 0.0584 AC: 206 AN: 3526

American (AMR) AF: 0.107 AC: 241 AN: 2254

Ashkenazi Jewish (ASJ) AF: 0.0431 AC: 206 AN: 4778

East Asian (EAS) AF: 0.0693 AC: 735 AN: 10610

South Asian (SAS) AF: 0.00912 AC: 6 AN: 658

European-Finnish (FIN) AF: 0.0233 AC: 11 AN: 472

Middle Eastern (MID) AF: 0.0536 AC: 25 AN: 466

European-Non Finnish (NFE) AF: 0.0129 AC: 599 AN: 46604

Other (OTH) AF: 0.0330 AC: 209 AN: 6328

GnomAD4 genome AF: 0.0421 AC: 6416 AN: 152242 Hom.: 256 Cov.: 33 AF XY: 0.0448 AC XY: 3336 AN XY: 74430

African (AFR) AF: 0.0668 AC: 2774 AN: 41528

American (AMR) AF: 0.103 AC: 1582 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0427 AC: 148 AN: 3470

East Asian (EAS) AF: 0.0930 AC: 481 AN: 5174

South Asian (SAS) AF: 0.0191 AC: 92 AN: 4826

European-Finnish (FIN) AF: 0.0342 AC: 363 AN: 10600

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0117 AC: 796 AN: 68030

Other (OTH) AF: 0.0498 AC: 105 AN: 2110

Alfa AF: 0.0235 Hom.: 12

Bravo AF: 0.0500

Asia WGS AF: 0.0660 AC: 229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.5
DANN	Benign	0.64
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs74999341; hg19: chr17-70121454; COSMIC: COSV55421894;