rs550338

Variant names:

• chr12-24359103-G-A
• rs550338
• NM_152989.5:c.-99+9460C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-24359103-G-A
• chr12-24359103-G-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.-99+9460C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,004 control chromosomes in the GnomAD database, including 8,707 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 (8707 hom., cov: 32)
• Consequence: SOX5 NM_152989.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX5	NM_152989.5	c.-99+9460C>T		intron_variant	Intron 3 of 17		NP_694534.1
SOX5	NM_001261414.3	c.-174+9460C>T		intron_variant	Intron 3 of 16		NP_001248343.1
SOX5	XM_011520835.3	c.-99+9460C>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.-174+9460C>T		intron_variant	Intron 3 of 16			ENSP00000493866.1
SOX5	ENST00000704300.1	c.-99+9460C>T		intron_variant	Intron 3 of 7			ENSP00000515824.1
SOX5	ENST00000446891.7	c.-174+9460C>T		intron_variant	Intron 2 of 4	5		ENSP00000494627.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47419 AN: 151882 Hom.: 8676 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.313 AC: 47505 AN: 152004 Hom.: 8707 Cov.: 32 AF XY: 0.328 AC XY: 24369 AN XY: 74306

African (AFR) AF: 0.297 AC: 12305 AN: 41454

American (AMR) AF: 0.477 AC: 7279 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 947 AN: 3472

East Asian (EAS) AF: 0.786 AC: 4066 AN: 5170

South Asian (SAS) AF: 0.535 AC: 2577 AN: 4814

European-Finnish (FIN) AF: 0.339 AC: 3584 AN: 10564

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15653 AN: 67940

Other (OTH) AF: 0.328 AC: 692 AN: 2110

Alfa AF: 0.266 Hom.: 11706

Bravo AF: 0.324

Asia WGS AF: 0.642 AC: 2233 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	1.7
DANN	Benign	0.32
PhyloP100		-0.22

Splicing

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

Other links and lift over

dbSNP: rs550338; hg19: chr12-24512037;