16-982060-G-T

Variant names:

• chr16-982060-G-T
• rs992606634
• NM_014587.5:c.138G>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_014587.5(SOX8):​c.138G>T​(p.Gly46Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000201 in 1,145,198 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. Synonymous variant affecting the same amino acid position (i.e. G46G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: SOX8 NM_014587.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325
• Publications: 0 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=-0.325 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 23 AD gene.

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.138G>T	p.Gly46Gly	synonymous	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.138G>T	p.Gly46Gly	synonymous	Exon 1 of 3	ENSP00000293894.3	P57073
	SOX8	ENST00000711628.1		c.138G>T	p.Gly46Gly	synonymous	Exon 1 of 3	ENSP00000518816.1	A0AAA9YHU3
	SOX8	ENST00000711625.1		c.138G>T	p.Gly46Gly	synonymous	Exon 1 of 3	ENSP00000518813.1	A0AAA9YHN4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000201 AC: 23 AN: 1145198 Hom.: 0 Cov.: 30 AF XY: 0.0000181 AC XY: 10 AN XY: 553608

African (AFR) AF: 0.00 AC: 0 AN: 22988

American (AMR) AF: 0.00 AC: 0 AN: 8632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14910

East Asian (EAS) AF: 0.00 AC: 0 AN: 26426

South Asian (SAS) AF: 0.00 AC: 0 AN: 34192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3126

European-Non Finnish (NFE) AF: 0.0000239 AC: 23 AN: 963872

Other (OTH) AF: 0.00 AC: 0 AN: 46274

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.6
DANN	Benign	0.71
PhyloP100		-0.33
PromoterAI		-0.013	Neutral

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: rs992606634; hg19: chr16-1032060;