rs200231150

Variant names:

• chr16-981954-C-A
• rs200231150
• NM_014587.5:c.32C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-981954-C-A
• chr16-981954-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014587.5(SOX8):​c.32C>A​(p.Pro11Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000028 in 1,427,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P11L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: SOX8 NM_014587.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• Publications: 3 publications found

Genes affected

SOX8 (HGNC:11203): (SRY-box transcription factor 8) 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 activator after forming a protein complex with other proteins. This protein may be involved in brain development and function. Haploinsufficiency for this protein may contribute to the cognitive disability found in an alpha-thalassemia-related syndrome (ART-16). This protein is also highly expressed in the majority of human hepatocellular carcinomas and promotes cellular proliferation and enhanced tumor growth. [provided by RefSeq, Jul 2017]

SOX8 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18083408).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014587.5. 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
	SOX8	NM_014587.5	MANE Select	c.32C>A	p.Pro11Gln	missense	Exon 1 of 3	NP_055402.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX8	ENST00000293894.4	TSL:1 MANE Select	c.32C>A	p.Pro11Gln	missense	Exon 1 of 3	ENSP00000293894.3	P57073
	SOX8	ENST00000711628.1		c.32C>A	p.Pro11Gln	missense	Exon 1 of 3	ENSP00000518816.1	A0AAA9YHU3
	SOX8	ENST00000711625.1		c.32C>A	p.Pro11Gln	missense	Exon 1 of 3	ENSP00000518813.1	A0AAA9YHN4

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 150362 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000485

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000157 AC: 2 AN: 1276968 Hom.: 0 Cov.: 30 AF XY: 0.00000158 AC XY: 1 AN XY: 633390

African (AFR) AF: 0.00 AC: 0 AN: 25932

American (AMR) AF: 0.00 AC: 0 AN: 27588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20708

East Asian (EAS) AF: 0.00 AC: 0 AN: 26884

South Asian (SAS) AF: 0.00 AC: 0 AN: 68784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3454

European-Non Finnish (NFE) AF: 9.79e-7 AC: 1 AN: 1021530

Other (OTH) AF: 0.0000198 AC: 1 AN: 50494

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 150362 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 73388

African (AFR) AF: 0.0000485 AC: 2 AN: 41232

American (AMR) AF: 0.00 AC: 0 AN: 15112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5114

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9936

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67402

Other (OTH) AF: 0.00 AC: 0 AN: 2064

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Benign	0.89
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.66	T
M_CAP	Pathogenic	0.80	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.8
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.097
Sift	Benign	0.38	T
Sift4G	Benign	0.17	T
Polyphen		0.24	B
Vest4		0.23
MutPred		0.16		Loss of catalytic residue at P11 (P = 0.0197)
MVP		0.47
MPC		1.9
ClinPred		0.28	T
GERP RS		3.4
PromoterAI		0.013	Neutral
Varity_R		0.11
gMVP		0.37
Mutation Taster		=91/9	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: rs200231150; hg19: chr16-1031954;