NM_006940.6:c.569-4367A>C

Variant names:

• chr12-23745406-T-G
• rs10771022
• NM_006940.6:c.569-4367A>C

Variant summary

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

The NM_006940.6(SOX5):​c.569-4367A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 151,930 control chromosomes in the GnomAD database, including 27,291 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 0.58 (27291 hom., cov: 32)
• Consequence: SOX5 NM_006940.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283
• Publications: 5 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

ENSG00000296429 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 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.569-4367A>C		intron	N/A	NP_008871.3
	SOX5	NM_001261415.3		c.539-4367A>C		intron	N/A	NP_001248344.1
	SOX5	NM_152989.5		c.530-4367A>C		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.569-4367A>C		intron	N/A	ENSP00000398273.2
	SOX5	ENST00000545921.5	TSL:2	c.539-4367A>C		intron	N/A	ENSP00000443520.1
	SOX5	ENST00000537393.5	TSL:5	c.464-4367A>C		intron	N/A	ENSP00000439832.1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88593 AN: 151810 Hom.: 27271 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.584 AC: 88664 AN: 151930 Hom.: 27291 Cov.: 32 AF XY: 0.580 AC XY: 43084 AN XY: 74238

African (AFR) AF: 0.383 AC: 15855 AN: 41412

American (AMR) AF: 0.657 AC: 10026 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2450 AN: 3464

East Asian (EAS) AF: 0.812 AC: 4193 AN: 5164

South Asian (SAS) AF: 0.588 AC: 2833 AN: 4818

European-Finnish (FIN) AF: 0.537 AC: 5668 AN: 10546

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.671 AC: 45582 AN: 67962

Other (OTH) AF: 0.588 AC: 1236 AN: 2102

Alfa AF: 0.653 Hom.: 62751

Bravo AF: 0.586

Asia WGS AF: 0.675 AC: 2346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.58
PhyloP100		0.28
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: rs10771022; hg19: chr12-23898340;