16-982163-T-A

Variant names:

• chr16-982163-T-A
• NM_014587.5:c.241T>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014587.5(SOX8):​c.241T>A​(p.Trp81Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SOX8 NM_014587.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.42

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.923

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX8	NM_014587.5	c.241T>A	p.Trp81Arg	missense_variant	Exon 1 of 3	ENST00000293894.4	NP_055402.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX8	ENST00000293894.4	c.241T>A	p.Trp81Arg	missense_variant	Exon 1 of 3	1	NM_014587.5	ENSP00000293894.3
SOX8	ENST00000566034.1	n.78T>A		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SOX8: PM2, PP2, PP3 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.90	D
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Pathogenic	0.98	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	2.9	M
PrimateAI	Pathogenic	0.96	D
PROVEAN	Pathogenic	-12	D
REVEL	Pathogenic	0.80
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.046	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.60		Gain of disorder (P = 0.0039);
MVP		0.88
MPC		4.3
ClinPred		0.99	D
GERP RS		3.1
Varity_R		0.94
gMVP		0.68

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: chr16-1032163;