13-112068208-G-A

Position:

• chr13-112068208-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005986.3(SOX1):​c.550G>A​(p.Val184Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SOX1 NM_005986.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.97

Genes affected

SOX1 (HGNC:11189): (SRY-box transcription factor 1) This intronless 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. In mice, a similar protein regulates the gamma-crystallin genes and is essential for lens development. [provided by RefSeq, Jul 2008]

SOX1-OT (HGNC:42733): (SOX1 overlapping transcript)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3508411).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX1	NM_005986.3	c.550G>A	p.Val184Ile	missense_variant	1/1	ENST00000330949.3	NP_005977.2
SOX1-OT	NR_120392.1	n.85-27267G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX1	ENST00000330949.3	c.550G>A	p.Val184Ile	missense_variant	1/1	6	NM_005986.3	ENSP00000330218.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 633958 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 301202

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2024

The c.550G>A (p.V184I) alteration is located in exon 1 (coding exon 1) of the SOX1 gene. This alteration results from a G to A substitution at nucleotide position 550, causing the valine (V) at amino acid position 184 to be replaced by an isoleucine (I). 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	Benign	0.21
BayesDel_addAF	Benign	0.0043	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.17	N
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.58	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	0.97	L
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.080	N
REVEL	Uncertain	0.32
Sift	Benign	0.046	D
Sift4G	Benign	0.20	T
Polyphen		0.97	D
Vest4		0.18
MutPred		0.38		Gain of catalytic residue at Y181 (P = 0.0041);
MVP		0.68
ClinPred		0.76	D
GERP RS		-0.0049
Varity_R		0.056
gMVP		0.37

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

LitVar

Other links and lift over

dbSNP: rs1432587806; hg19: chr13-112722522;