12-23584632-G-A

Variant names:

• chr12-23584632-G-A
• rs11046992
• NM_006940.6:c.1165-8794C>T

Variant summary

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

The NM_006940.6(SOX5):​c.1165-8794C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,558,052 control chromosomes in the GnomAD database, including 63,769 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 0.24 (4881 hom., cov: 32)
  • Exomes 𝑓: 0.28 (58888 hom.)
• Consequence: SOX5 NM_006940.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.800
• Publications: 14 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.301 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.1165-8794C>T		intron	N/A	NP_008871.3
	SOX5	NM_001261415.3		c.1135-8794C>T		intron	N/A	NP_001248344.1
	SOX5	NM_152989.5		c.1126-8794C>T		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.1165-8794C>T		intron	N/A	ENSP00000398273.2
	SOX5	ENST00000545921.5	TSL:2	c.1135-8794C>T		intron	N/A	ENSP00000443520.1
	SOX5	ENST00000537393.5	TSL:5	c.1060-8794C>T		intron	N/A	ENSP00000439832.1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35776 AN: 151862 Hom.: 4880 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.247

GnomAD4 exome AF: 0.285 AC: 400552 AN: 1406072 Hom.: 58888 Cov.: 24 AF XY: 0.286 AC XY: 200956 AN XY: 702616

African (AFR) AF: 0.0940 AC: 3044 AN: 32390

American (AMR) AF: 0.141 AC: 6236 AN: 44366

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 10106 AN: 25626

East Asian (EAS) AF: 0.294 AC: 11606 AN: 39412

South Asian (SAS) AF: 0.282 AC: 23911 AN: 84940

European-Finnish (FIN) AF: 0.329 AC: 16147 AN: 49130

Middle Eastern (MID) AF: 0.322 AC: 1817 AN: 5644

European-Non Finnish (NFE) AF: 0.291 AC: 310369 AN: 1065962

Other (OTH) AF: 0.295 AC: 17316 AN: 58602

GnomAD4 genome AF: 0.236 AC: 35799 AN: 151980 Hom.: 4881 Cov.: 32 AF XY: 0.238 AC XY: 17711 AN XY: 74286

African (AFR) AF: 0.101 AC: 4172 AN: 41494

American (AMR) AF: 0.188 AC: 2871 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1365 AN: 3468

East Asian (EAS) AF: 0.314 AC: 1621 AN: 5160

South Asian (SAS) AF: 0.281 AC: 1357 AN: 4822

European-Finnish (FIN) AF: 0.342 AC: 3606 AN: 10542

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19736 AN: 67932

Other (OTH) AF: 0.252 AC: 533 AN: 2112

Alfa AF: 0.262 Hom.: 15794

Bravo AF: 0.217

Asia WGS AF: 0.276 AC: 963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.42
PhyloP100		-0.80
PromoterAI		0.0033	Neutral
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: rs11046992; hg19: chr12-23737566; COSMIC: COSV58630620; COSMIC: COSV58630620;