NM_003107.3:c.63C>G

Variant names:

• chr6-21594597-C-G
• rs201097197
• NM_003107.3:c.63C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_003107.3(SOX4):​c.63C>G​(p.Asp21Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,608,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SOX4 NM_003107.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• Publications: 1 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.31380618).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

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.63C>G	p.Asp21Glu	missense	Exon 1 of 1	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.63C>G	p.Asp21Glu	missense	Exon 1 of 1	ENSP00000244745.1	Q06945
	LINC00581	ENST00000637901.1	TSL:5	n.168+829G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1456732 Hom.: 0 Cov.: 32 AF XY: 0.00000552 AC XY: 4 AN XY: 724410

African (AFR) AF: 0.00 AC: 0 AN: 33396

American (AMR) AF: 0.0000225 AC: 1 AN: 44514

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26036

East Asian (EAS) AF: 0.00 AC: 0 AN: 39538

South Asian (SAS) AF: 0.00 AC: 0 AN: 85916

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5174

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1110718

Other (OTH) AF: 0.00 AC: 0 AN: 60056

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152212 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74350

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.65	D
Eigen	Benign	-0.057
Eigen_PC	Benign	0.047
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.65	D
MetaRNN	Benign	0.31	T
MetaSVM	Uncertain	0.50	D
MutationAssessor	Benign	0.30	N
PhyloP100		1.5
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.40
Sift	Benign	0.17	T
Sift4G	Benign	0.16	T
Polyphen		0.33	B
Vest4		0.15
MutPred		0.20		Loss of helix (P = 0.079)
MVP		0.90
MPC		1.1
ClinPred		0.83	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.27
gMVP		0.89
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs201097197; hg19: chr6-21594828;