12-23729549-G-C

Variant names:

• chr12-23729549-G-C
• rs989278
• NM_006940.6:c.810+5135C>G

Variant summary

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

The NM_006940.6(SOX5):​c.810+5135C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 152,070 control chromosomes in the GnomAD database, including 43,319 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 0.75 (43319 hom., cov: 33)
• Consequence: SOX5 NM_006940.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• Publications: 2 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: G2P, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae)
• 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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006940.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX5	NM_006940.6	MANE Select	c.810+5135C>G		intron	N/A	NP_008871.3
	SOX5	NM_001261415.3		c.780+5135C>G		intron	N/A	NP_001248344.1	P35711-5
	SOX5	NM_152989.5		c.771+5135C>G		intron	N/A	NP_694534.1	T2CYZ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX5	ENST00000451604.7	TSL:1 MANE Select	c.810+5135C>G		intron	N/A	ENSP00000398273.2	P35711-1
	SOX5	ENST00000900854.1		c.810+5135C>G		intron	N/A	ENSP00000570913.1
	SOX5	ENST00000900855.1		c.810+5135C>G		intron	N/A	ENSP00000570914.1

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114642 AN: 151952 Hom.: 43293 Cov.: 33

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.754 AC: 114720 AN: 152070 Hom.: 43319 Cov.: 33 AF XY: 0.752 AC XY: 55884 AN XY: 74350

African (AFR) AF: 0.737 AC: 30567 AN: 41486

American (AMR) AF: 0.741 AC: 11315 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2600 AN: 3470

East Asian (EAS) AF: 0.787 AC: 4052 AN: 5146

South Asian (SAS) AF: 0.721 AC: 3479 AN: 4824

European-Finnish (FIN) AF: 0.753 AC: 7971 AN: 10592

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.770 AC: 52362 AN: 67974

Other (OTH) AF: 0.722 AC: 1524 AN: 2112

Alfa AF: 0.720 Hom.: 2178

Bravo AF: 0.750

Asia WGS AF: 0.746 AC: 2591 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		-0.20
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: rs989278; hg19: chr12-23882483;