12-24187307-T-C

Variant names:

• chr12-24187307-T-C
• rs7973385
• NM_152989.5:c.-2+89909A>G

Variant summary

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

The NM_152989.5(SOX5):​c.-2+89909A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,122 control chromosomes in the GnomAD database, including 15,662 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 0.44 (15662 hom., cov: 33)
• Consequence: SOX5 NM_152989.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX5	NM_152989.5	c.-2+89909A>G		intron_variant	Intron 4 of 17		NP_694534.1
SOX5	NM_001261414.3	c.-2+26036A>G		intron_variant	Intron 5 of 16		NP_001248343.1
SOX5	XM_011520835.3	c.-2+89909A>G		intron_variant	Intron 4 of 17		XP_011519137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX5	ENST00000646273.1	c.-2+26036A>G		intron_variant	Intron 5 of 16			ENSP00000493866.1
SOX5	ENST00000704300.1	c.-2+89909A>G		intron_variant	Intron 4 of 7			ENSP00000515824.1
SOX5	ENST00000536729.2	c.-2+26036A>G		intron_variant	Intron 3 of 4	5		ENSP00000496161.1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67605 AN: 152004 Hom.: 15653 Cov.: 33

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.445 AC: 67630 AN: 152122 Hom.: 15662 Cov.: 33 AF XY: 0.439 AC XY: 32654 AN XY: 74372

African (AFR) AF: 0.367 AC: 15239 AN: 41502

American (AMR) AF: 0.436 AC: 6667 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1851 AN: 3472

East Asian (EAS) AF: 0.166 AC: 860 AN: 5180

South Asian (SAS) AF: 0.385 AC: 1858 AN: 4820

European-Finnish (FIN) AF: 0.433 AC: 4582 AN: 10574

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35189 AN: 67972

Other (OTH) AF: 0.463 AC: 980 AN: 2116

Alfa AF: 0.497 Hom.: 9648

Bravo AF: 0.438

Asia WGS AF: 0.306 AC: 1068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.096
DANN	Benign	0.40
PhyloP100		-0.28

Splicing

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

Other links and lift over

dbSNP: rs7973385; hg19: chr12-24340241;