rs11047102

Variant names:

• chr12-23793212-C-T
• rs11047102
• NM_006940.6:c.482-37488G>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.482-37488G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.079 in 152,066 control chromosomes in the GnomAD database, including 603 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 0.079 (603 hom., cov: 31)
• Consequence: SOX5 NM_006940.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 20 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.109 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.482-37488G>A		intron	N/A	NP_008871.3
	SOX5	NM_001261415.3		c.452-37488G>A		intron	N/A	NP_001248344.1	P35711-5
	SOX5	NM_152989.5		c.443-37488G>A		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.482-37488G>A		intron	N/A	ENSP00000398273.2	P35711-1
	SOX5	ENST00000900854.1		c.482-37488G>A		intron	N/A	ENSP00000570913.1
	SOX5	ENST00000900855.1		c.482-37488G>A		intron	N/A	ENSP00000570914.1

Frequencies

GnomAD3 genomes AF: 0.0791 AC: 12014 AN: 151948 Hom.: 600 Cov.: 31

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.0245

Gnomad SAS AF: 0.0500

Gnomad FIN AF: 0.0982

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0941

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

GnomAD4 genome AF: 0.0790 AC: 12017 AN: 152066 Hom.: 603 Cov.: 31 AF XY: 0.0782 AC XY: 5813 AN XY: 74320

African (AFR) AF: 0.0213 AC: 883 AN: 41478

American (AMR) AF: 0.113 AC: 1729 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 501 AN: 3470

East Asian (EAS) AF: 0.0246 AC: 127 AN: 5172

South Asian (SAS) AF: 0.0490 AC: 236 AN: 4814

European-Finnish (FIN) AF: 0.0982 AC: 1037 AN: 10562

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7089 AN: 67982

Other (OTH) AF: 0.0926 AC: 196 AN: 2116

Alfa AF: 0.0979 Hom.: 642

Bravo AF: 0.0810

Asia WGS AF: 0.0430 AC: 150 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.39
PhyloP100		-0.033
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: rs11047102; hg19: chr12-23946146;