rs7311001

Variant names:

• chr12-23610248-A-T
• rs7311001
• NM_006940.6:c.1018-5715T>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.1018-5715T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 151,938 control chromosomes in the GnomAD database, including 7,287 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 0.31 (7287 hom., cov: 32)
• Consequence: SOX5 NM_006940.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322
• Publications: 0 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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.309 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.1018-5715T>A		intron	N/A	NP_008871.3
	SOX5	NM_001261415.3		c.988-5715T>A		intron	N/A	NP_001248344.1	P35711-5
	SOX5	NM_152989.5		c.979-5715T>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.1018-5715T>A		intron	N/A	ENSP00000398273.2	P35711-1
	SOX5	ENST00000900854.1		c.1018-5715T>A		intron	N/A	ENSP00000570913.1
	SOX5	ENST00000900855.1		c.1018-5715T>A		intron	N/A	ENSP00000570914.1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46423 AN: 151820 Hom.: 7284 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.306 AC: 46463 AN: 151938 Hom.: 7287 Cov.: 32 AF XY: 0.306 AC XY: 22715 AN XY: 74252

African (AFR) AF: 0.313 AC: 12991 AN: 41458

American (AMR) AF: 0.260 AC: 3961 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1569 AN: 3466

East Asian (EAS) AF: 0.314 AC: 1618 AN: 5158

South Asian (SAS) AF: 0.317 AC: 1530 AN: 4822

European-Finnish (FIN) AF: 0.275 AC: 2910 AN: 10570

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

European-Non Finnish (NFE) AF: 0.304 AC: 20639 AN: 67914

Other (OTH) AF: 0.309 AC: 652 AN: 2108

Alfa AF: 0.291 Hom.: 837

Bravo AF: 0.303

Asia WGS AF: 0.360 AC: 1252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.5
DANN	Benign	0.92
PhyloP100		0.32
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: rs7311001; hg19: chr12-23763182;