rs59569785

Variant names:

• chr12-23618801-C-T
• rs59569785
• NM_006940.6:c.1018-14268G>A

Variant summary

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

The NM_006940.6(SOX5):​c.1018-14268G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,078 control chromosomes in the GnomAD database, including 2,481 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 0.17 (2481 hom., cov: 32)
• Consequence: SOX5 NM_006940.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX5	NM_006940.6	MANE Select	c.1018-14268G>A		intron	N/A	NP_008871.3
	SOX5	NM_001261415.3		c.988-14268G>A		intron	N/A	NP_001248344.1
	SOX5	NM_152989.5		c.979-14268G>A		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.1018-14268G>A		intron	N/A	ENSP00000398273.2
	SOX5	ENST00000545921.5	TSL:2	c.988-14268G>A		intron	N/A	ENSP00000443520.1
	SOX5	ENST00000537393.5	TSL:5	c.913-14268G>A		intron	N/A	ENSP00000439832.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25928 AN: 151960 Hom.: 2479 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0636

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.171 AC: 25937 AN: 152078 Hom.: 2481 Cov.: 32 AF XY: 0.167 AC XY: 12426 AN XY: 74326

African (AFR) AF: 0.239 AC: 9909 AN: 41480

American (AMR) AF: 0.148 AC: 2259 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 489 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5178

South Asian (SAS) AF: 0.0641 AC: 309 AN: 4824

European-Finnish (FIN) AF: 0.173 AC: 1826 AN: 10570

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10468 AN: 67996

Other (OTH) AF: 0.186 AC: 392 AN: 2112

Alfa AF: 0.173 Hom.: 370

Bravo AF: 0.175

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.045
DANN	Benign	0.28
PhyloP100		-2.3
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: rs59569785; hg19: chr12-23771735;