rs565934

Variant names:

• chr12-24300519-G-A
• rs565934
• NM_152989.5:c.-98-23207C>T

Variant summary

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

The NM_152989.5(SOX5):​c.-98-23207C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,088 control chromosomes in the GnomAD database, including 1,565 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 0.14 (1565 hom., cov: 32)
• Consequence: SOX5 NM_152989.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.562
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX5	NM_152989.5	c.-98-23207C>T		intron_variant	Intron 3 of 17		NP_694534.1
SOX5	NM_001261414.3	c.-173-23207C>T		intron_variant	Intron 3 of 16		NP_001248343.1
SOX5	XM_011520835.3	c.-98-23207C>T		intron_variant	Intron 3 of 17		XP_011519137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX5	ENST00000646273.1	c.-173-23207C>T		intron_variant	Intron 3 of 16			ENSP00000493866.1
SOX5	ENST00000704300.1	c.-98-23207C>T		intron_variant	Intron 3 of 7			ENSP00000515824.1
SOX5	ENST00000536729.2	c.-173-23207C>T		intron_variant	Intron 1 of 4	5		ENSP00000496161.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21027 AN: 151970 Hom.: 1562 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.138 AC: 21023 AN: 152088 Hom.: 1565 Cov.: 32 AF XY: 0.141 AC XY: 10515 AN XY: 74314

African (AFR) AF: 0.130 AC: 5392 AN: 41496

American (AMR) AF: 0.109 AC: 1662 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 465 AN: 3468

East Asian (EAS) AF: 0.131 AC: 680 AN: 5184

South Asian (SAS) AF: 0.178 AC: 856 AN: 4810

European-Finnish (FIN) AF: 0.213 AC: 2240 AN: 10526

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9361 AN: 67994

Other (OTH) AF: 0.130 AC: 275 AN: 2116

Alfa AF: 0.136 Hom.: 4357

Bravo AF: 0.127

Asia WGS AF: 0.151 AC: 525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	13
DANN	Benign	0.77
PhyloP100		0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs565934; hg19: chr12-24453453;