rs7305773

Variant names:

• chr12-23818252-T-C
• rs7305773
• NM_006940.6:c.481+27731A>G

Variant summary

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

The ENST00000451604.7(SOX5):​c.481+27731A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,198 control chromosomes in the GnomAD database, including 1,139 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 0.11 (1139 hom., cov: 32)
• Consequence: SOX5 ENST00000451604.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425
• Publications: 1 publications found

Genes affected

SOX5 (HGNC:11201): (SRY-box transcription factor 5) This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins. The encoded protein may play a role in chondrogenesis. A pseudogene of this gene is located on chromosome 8. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

SOX5 Gene-Disease associations (from GenCC):

• Lamb-Shaffer syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• developmental and speech delay due to SOX5 deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000451604.7. 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
	SOX5	NM_006940.6	MANE Select	c.481+27731A>G		intron	N/A	NP_008871.3
	SOX5	NM_001261415.3		c.451+27731A>G		intron	N/A	NP_001248344.1
	SOX5	NM_152989.5		c.442+27731A>G		intron	N/A	NP_694534.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX5	ENST00000451604.7	TSL:1 MANE Select	c.481+27731A>G		intron	N/A	ENSP00000398273.2
	SOX5	ENST00000545921.5	TSL:2	c.451+27731A>G		intron	N/A	ENSP00000443520.1
	SOX5	ENST00000537393.5	TSL:5	c.376+27731A>G		intron	N/A	ENSP00000439832.1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17444 AN: 152080 Hom.: 1136 Cov.: 32

Gnomad AFR AF: 0.0766

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0715

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0976

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.0976

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.115 AC: 17457 AN: 152198 Hom.: 1139 Cov.: 32 AF XY: 0.115 AC XY: 8523 AN XY: 74386

African (AFR) AF: 0.0769 AC: 3194 AN: 41540

American (AMR) AF: 0.0713 AC: 1090 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5182

South Asian (SAS) AF: 0.0972 AC: 469 AN: 4824

European-Finnish (FIN) AF: 0.152 AC: 1607 AN: 10582

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 292

European-Non Finnish (NFE) AF: 0.153 AC: 10372 AN: 68002

Other (OTH) AF: 0.0966 AC: 204 AN: 2112

Alfa AF: 0.139 Hom.: 2546

Bravo AF: 0.106

Asia WGS AF: 0.0430 AC: 152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.59
PhyloP100		0.42
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: rs7305773; hg19: chr12-23971186;