6-21594625-GC-AA

Position:

• chr6-21594625-GC-AA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003107.3(SOX4):​c.91_92delinsAA​(p.Ala31Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SOX4 NM_003107.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.03

Genes affected

SOX4 (HGNC:11200): (SRY-box transcription factor 4) This intronless 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, such as syndecan binding protein (syntenin). The protein may function in the apoptosis pathway leading to cell death as well as to tumorigenesis and may mediate downstream effects of parathyroid hormone (PTH) and PTH-related protein (PTHrP) in bone development. The solution structure has been resolved for the HMG-box of a similar mouse protein. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX4	NM_003107.3	c.91_92delinsAA	p.Ala31Asn	missense_variant	1/1	ENST00000244745.4	NP_003098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX4	ENST00000244745.4	c.91_92delinsAA	p.Ala31Asn	missense_variant	1/1		NM_003107.3	ENSP00000244745	P1
	ENST00000637901.1	n.168+800_168+801delinsTT		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Coffin-Siris syndrome 10 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetics and Molecular Pathology, SA Pathology

Jul 20, 2023

The SOX4 c.91_92delGCinsAA variant is classified as a VARIANT of UNCERTAIN SIGNIFICANCE (PS2, PM2, BP4) The SOX4 c.91_92delGCinsAA variant is a single nucleotide change in exon 1/1 of the SOX4 gene, which is predicted to change the amino acid alanine at position 31 in the protein to asparagine. This variant has been identified as a de novo variant in this patient (PS2). This variant is absent from population databases (PM2). Multiple lines of computational evidence suggest this variant has no impact on the gene or gene product (BP4). This variant has not been reported in dbSNP, ClinVar or HGMD. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-21594856;