chr16-981964-C-T

Variant names:

• chr16-981964-C-T
• rs201357577
• NM_014587.5:c.42C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_014587.5(SOX8):​c.42C>T​(p.Ser14Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 1,439,036 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (8 hom.)
• Consequence: SOX8 NM_014587.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.860
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 16-981964-C-T is Benign according to our data. Variant chr16-981964-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 713378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.86 with no splicing effect.
• BS2: High AC in GnomAd4 at 379 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.42C>T	p.Ser14Ser	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.42C>T	p.Ser14Ser	synonymous	Exon 1 of 3	ENSP00000293894.3	P57073
	SOX8	ENST00000711628.1		c.42C>T	p.Ser14Ser	synonymous	Exon 1 of 3	ENSP00000518816.1	A0AAA9YHU3
	SOX8	ENST00000711625.1		c.42C>T	p.Ser14Ser	synonymous	Exon 1 of 3	ENSP00000518813.1	A0AAA9YHN4

Frequencies

GnomAD3 genomes AF: 0.00252 AC: 379 AN: 150546 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000363

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.00238

Gnomad ASJ AF: 0.00203

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00451

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00368

Gnomad OTH AF: 0.00243

GnomAD2 exomes AF: 0.00293 AC: 368 AN: 125426 AF XY: 0.00297

Gnomad AFR exome AF: 0.000424

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.00197

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00436

Gnomad NFE exome AF: 0.00484

Gnomad OTH exome AF: 0.00206

GnomAD4 exome AF: 0.00283 AC: 3651 AN: 1288382 Hom.: 8 Cov.: 30 AF XY: 0.00288 AC XY: 1843 AN XY: 639390

African (AFR) AF: 0.000914 AC: 24 AN: 26250

American (AMR) AF: 0.00188 AC: 54 AN: 28778

Ashkenazi Jewish (ASJ) AF: 0.00166 AC: 35 AN: 21132

East Asian (EAS) AF: 0.00 AC: 0 AN: 27232

South Asian (SAS) AF: 0.0000426 AC: 3 AN: 70422

European-Finnish (FIN) AF: 0.00455 AC: 146 AN: 32100

Middle Eastern (MID) AF: 0.000569 AC: 2 AN: 3512

European-Non Finnish (NFE) AF: 0.00320 AC: 3294 AN: 1027844

Other (OTH) AF: 0.00182 AC: 93 AN: 51112

GnomAD4 genome AF: 0.00252 AC: 379 AN: 150654 Hom.: 0 Cov.: 33 AF XY: 0.00251 AC XY: 185 AN XY: 73598

African (AFR) AF: 0.000362 AC: 15 AN: 41402

American (AMR) AF: 0.00238 AC: 36 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.00203 AC: 7 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5120

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00451 AC: 45 AN: 9978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00368 AC: 248 AN: 67436

Other (OTH) AF: 0.00240 AC: 5 AN: 2082

Alfa AF: 0.00381 Hom.: 0

Bravo AF: 0.00212

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Benign	0.84
PhyloP100		0.86
PromoterAI		0.0062	Neutral
Mutation Taster		=85/15	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: rs201357577; hg19: chr16-1031964;