rs1396208

Variant names:

• chr12-24405386-C-A
• rs1396208
• NM_152989.5:c.-176+2099G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-24405386-C-A
• chr12-24405386-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152989.5(SOX5):​c.-176+2099G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: SOX5 NM_152989.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.887
• 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: 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152989.5. 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_152989.5		c.-176+2099G>T		intron	N/A	NP_694534.1	T2CYZ2
	SOX5	NM_001261414.3		c.-251+2099G>T		intron	N/A	NP_001248343.1	P35711-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX5	ENST00000646273.1		c.-251+2099G>T		intron	N/A	ENSP00000493866.1	P35711-4
	SOX5	ENST00000704300.1		c.-176+2099G>T		intron	N/A	ENSP00000515824.1	A0A994J4I4
	SOX5	ENST00000446891.7	TSL:5	c.-250-36747G>T		intron	N/A	ENSP00000494627.1	A0A2R8Y5Q1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 21564

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.48
DANN	Benign	0.55
PhyloP100		-0.89

Splicing

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

Other links and lift over

dbSNP: rs1396208; hg19: chr12-24558320;