6-21594625-GC-AA

Variant names:

• chr6-21594625-GC-AA
• NM_003107.3:c.91_92delGCinsAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_003107.3(SOX4):​c.91_92delGCinsAA​(p.Ala31Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 0 publications found

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]

LINC00581 (HGNC:43840): (long intergenic non-protein coding RNA 581)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003107.3. 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
	SOX4	NM_003107.3	MANE Select	c.91_92delGCinsAA	p.Ala31Asn	missense	N/A	NP_003098.1	Q06945

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX4	ENST00000244745.4	TSL:6 MANE Select	c.91_92delGCinsAA	p.Ala31Asn	missense	N/A	ENSP00000244745.1	Q06945
	LINC00581	ENST00000637901.1	TSL:5	n.168+800_168+801delGCinsTT		intron	N/A

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

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Coffin-Siris syndrome 10 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.0

Splicing

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

Other links and lift over

hg19: chr6-21594856;