12-23700135-T-C

Variant names:

• chr12-23700135-T-C
• rs725124
• NM_006940.6:c.810+34549A>G

Variant summary

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

The NM_006940.6(SOX5):​c.810+34549A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,968 control chromosomes in the GnomAD database, including 12,937 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 0.40 (12937 hom., cov: 32)
• Consequence: SOX5 NM_006940.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100
• Publications: 4 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 (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX5	NM_006940.6	c.810+34549A>G		intron_variant	Intron 6 of 14	ENST00000451604.7	NP_008871.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX5	ENST00000451604.7	c.810+34549A>G		intron_variant	Intron 6 of 14	1	NM_006940.6	ENSP00000398273.2

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60926 AN: 151848 Hom.: 12920 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.401 AC: 60983 AN: 151968 Hom.: 12937 Cov.: 32 AF XY: 0.398 AC XY: 29602 AN XY: 74284

African (AFR) AF: 0.553 AC: 22910 AN: 41432

American (AMR) AF: 0.295 AC: 4494 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1146 AN: 3468

East Asian (EAS) AF: 0.229 AC: 1185 AN: 5172

South Asian (SAS) AF: 0.269 AC: 1297 AN: 4820

European-Finnish (FIN) AF: 0.427 AC: 4517 AN: 10572

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.355 AC: 24138 AN: 67952

Other (OTH) AF: 0.380 AC: 800 AN: 2108

Alfa AF: 0.358 Hom.: 44301

Bravo AF: 0.397

Asia WGS AF: 0.255 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.72
PhyloP100		-0.10
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: rs725124; hg19: chr12-23853069;