chr12-23672363-T-C

Variant names:

• chr12-23672363-T-C
• rs7970223
• NM_006940.6:c.811-6799A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006940.6(SOX5):​c.811-6799A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,176 control chromosomes in the GnomAD database, including 56,872 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 0.86 (56872 hom., cov: 31)
• Consequence: SOX5 NM_006940.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX5	NM_006940.6	c.811-6799A>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.811-6799A>G		intron_variant	Intron 6 of 14	1	NM_006940.6	ENSP00000398273.2

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131336 AN: 152058 Hom.: 56814 Cov.: 31

Gnomad AFR AF: 0.883

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.937

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.847

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

GnomAD4 genome AF: 0.864 AC: 131451 AN: 152176 Hom.: 56872 Cov.: 31 AF XY: 0.866 AC XY: 64401 AN XY: 74376

African (AFR) AF: 0.883 AC: 36667 AN: 41522

American (AMR) AF: 0.873 AC: 13343 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 2879 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5164 AN: 5172

South Asian (SAS) AF: 0.937 AC: 4515 AN: 4818

European-Finnish (FIN) AF: 0.809 AC: 8572 AN: 10600

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.845 AC: 57488 AN: 68000

Other (OTH) AF: 0.849 AC: 1787 AN: 2106

Alfa AF: 0.852 Hom.: 177159

Bravo AF: 0.867

Asia WGS AF: 0.969 AC: 3368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.83
PhyloP100		1.5
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: rs7970223; hg19: chr12-23825297;