rs6487366

Variant names:

• chr12-23950416-G-C
• rs6487366
• XM_011520832.3:c.109C>G

Variant summary

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

The XM_011520832.3(SOX5):​c.109C>G​(p.Arg37Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,004 control chromosomes in the GnomAD database, including 27,782 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (27782 hom., cov: 32)
• Consequence: SOX5 XM_011520832.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.595
• Publications: 7 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=-0.54).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX5	XM_011520832.3	c.109C>G	p.Arg37Gly	missense_variant	Exon 1 of 16		XP_011519134.2
SOX5	XM_047429451.1	c.109C>G	p.Arg37Gly	missense_variant	Exon 1 of 16		XP_047285407.1
SOX5	XM_017019888.2	c.109C>G	p.Arg37Gly	missense_variant	Exon 1 of 16		XP_016875377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX5	ENST00000545921.5	c.8+453C>G		intron_variant	Intron 1 of 14	2		ENSP00000443520.1
SOX5	ENST00000704299.1	c.-119-6128C>G		intron_variant	Intron 1 of 15			ENSP00000515823.1
SOX5	ENST00000646273.1	c.-1-54392C>G		intron_variant	Intron 5 of 16			ENSP00000493866.1

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90717 AN: 151886 Hom.: 27774 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.597 AC: 90747 AN: 152004 Hom.: 27782 Cov.: 32 AF XY: 0.588 AC XY: 43671 AN XY: 74270

African (AFR) AF: 0.576 AC: 23871 AN: 41446

American (AMR) AF: 0.499 AC: 7615 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2030 AN: 3468

East Asian (EAS) AF: 0.265 AC: 1370 AN: 5162

South Asian (SAS) AF: 0.396 AC: 1909 AN: 4820

European-Finnish (FIN) AF: 0.647 AC: 6827 AN: 10548

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45116 AN: 67974

Other (OTH) AF: 0.594 AC: 1253 AN: 2110

Alfa AF: 0.644 Hom.: 3950

Bravo AF: 0.585

Asia WGS AF: 0.393 AC: 1367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		0.59
PromoterAI		0.044	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6487366; hg19: chr12-24103350;