rs16926727

Variant names:

• chr12-23799411-A-G
• rs16926727
• NM_006940.6:c.482-43687T>C

Variant summary

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

The NM_006940.6(SOX5):​c.482-43687T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,010 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 0.12 (1139 hom., cov: 32)
• Consequence: SOX5 NM_006940.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.685
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX5	NM_006940.6	c.482-43687T>C		intron_variant	Intron 3 of 14	ENST00000451604.7	NP_008871.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX5	ENST00000451604.7	c.482-43687T>C		intron_variant	Intron 3 of 14	1	NM_006940.6	ENSP00000398273.2

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17594 AN: 151892 Hom.: 1137 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.0706

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0870

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.116 AC: 17619 AN: 152010 Hom.: 1139 Cov.: 32 AF XY: 0.120 AC XY: 8892 AN XY: 74300

African (AFR) AF: 0.125 AC: 5202 AN: 41518

American (AMR) AF: 0.167 AC: 2545 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 450 AN: 3470

East Asian (EAS) AF: 0.207 AC: 1070 AN: 5166

South Asian (SAS) AF: 0.0711 AC: 343 AN: 4826

European-Finnish (FIN) AF: 0.162 AC: 1714 AN: 10594

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0870 AC: 5905 AN: 67872

Other (OTH) AF: 0.131 AC: 276 AN: 2106

Alfa AF: 0.0960 Hom.: 3255

Bravo AF: 0.118

Asia WGS AF: 0.154 AC: 535 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.25
DANN	Benign	0.35
PhyloP100		-0.69
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: rs16926727; hg19: chr12-23952345;