chr6-21594590-G-C

Position:

• chr6-21594590-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003107.3(SOX4):​c.56G>C​(p.Ser19Thr) variant causes a missense 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. 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: 2.88

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25757134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX4	NM_003107.3	c.56G>C	p.Ser19Thr	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.56G>C	p.Ser19Thr	missense_variant	1/1		NM_003107.3	ENSP00000244745	P1
	ENST00000637901.1	n.168+836C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2023

The c.56G>C (p.S19T) alteration is located in exon 1 (coding exon 1) of the SOX4 gene. This alteration results from a G to C substitution at nucleotide position 56, causing the serine (S) at amino acid position 19 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Benign	0.90
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.57	T
M_CAP	Pathogenic	0.78	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	0.50	D;D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.33
Sift	Benign	0.27	T
Sift4G	Benign	0.51	T
Polyphen		0.34	B
Vest4		0.069
MutPred		0.14		Gain of glycosylation at S19 (P = 0.1162);
MVP		0.86
MPC		0.90
ClinPred		0.50	D
GERP RS		3.3
Varity_R		0.27
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: chr6-21594821;