16-982181-C-G

Variant names:

• chr16-982181-C-G
• NM_014587.5:c.259C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014587.5(SOX8):​c.259C>G​(p.Pro87Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 4.39

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX8	NM_014587.5	c.259C>G	p.Pro87Ala	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.259C>G	p.Pro87Ala	missense_variant	Exon 1 of 3	1	NM_014587.5	ENSP00000293894.3
SOX8	ENST00000566034.1	n.96C>G		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 specified Uncertain:1

Sep 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.259C>G (p.P87A) alteration is located in exon 1 (coding exon 1) of the SOX8 gene. This alteration results from a C to G substitution at nucleotide position 259, causing the proline (P) at amino acid position 87 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.74	D
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.76	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Uncertain	0.65	D
MutationAssessor	Uncertain	2.9	M
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-6.5	D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.97	D
Vest4		0.23
MutPred		0.56		Gain of MoRF binding (P = 0.032);
MVP		0.73
MPC		2.8
ClinPred		0.99	D
GERP RS		3.1
Varity_R		0.76
gMVP		0.61

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: chr16-1032181;