chr13-112068343-GCGCACC-G

Position:

• chr13-112068343-GCGCACC-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_005986.3(SOX1):​c.698_703del​(p.Pro233_His234del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00186 in 1,215,636 control chromosomes in the GnomAD database, including 14 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (12 hom.)
• Consequence: SOX1 NM_005986.3 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.97

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 13-112068343-GCGCACC-G is Benign according to our data. Variant chr13-112068343-GCGCACC-G is described in ClinVar as [Likely_benign]. Clinvar id is 2643961.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX1	NM_005986.3	c.698_703del	p.Pro233_His234del	inframe_deletion	1/1	ENST00000330949.3
SOX1-OT	NR_120392.1	n.85-27119_85-27114del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX1	ENST00000330949.3	c.698_703del	p.Pro233_His234del	inframe_deletion	1/1		NM_005986.3	P1
SOX1-OT	ENST00000658904.1	n.168+11173_168+11178del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00177 AC: 253 AN: 143160 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000252

Gnomad AMI AF: 0.00792

Gnomad AMR AF: 0.000962

Gnomad ASJ AF: 0.00386

Gnomad EAS AF: 0.000423

Gnomad SAS AF: 0.00877

Gnomad FIN AF: 0.000244

Gnomad MID AF: 0.00347

Gnomad NFE AF: 0.00244

Gnomad OTH AF: 0.00254

GnomAD3 exomes AF: 0.00299 AC: 187 AN: 62564 Hom.: 2 AF XY: 0.00356 AC XY: 132 AN XY: 37096

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00357

Gnomad EAS exome AF: 0.00107

Gnomad SAS exome AF: 0.00712

Gnomad FIN exome AF: 0.000431

Gnomad NFE exome AF: 0.00178

Gnomad OTH exome AF: 0.00441

GnomAD4 exome AF: 0.00187 AC: 2008 AN: 1072406 Hom.: 12 AF XY: 0.00208 AC XY: 1096 AN XY: 526884

Gnomad4 AFR exome AF: 0.000498

Gnomad4 AMR exome AF: 0.000962

Gnomad4 ASJ exome AF: 0.00412

Gnomad4 EAS exome AF: 0.000229

Gnomad4 SAS exome AF: 0.00863

Gnomad4 FIN exome AF: 0.000547

Gnomad4 NFE exome AF: 0.00149

Gnomad4 OTH exome AF: 0.00200

GnomAD4 genome AF: 0.00177 AC: 253 AN: 143230 Hom.: 2 Cov.: 32 AF XY: 0.00195 AC XY: 136 AN XY: 69672

Gnomad4 AFR AF: 0.000252

Gnomad4 AMR AF: 0.000961

Gnomad4 ASJ AF: 0.00386

Gnomad4 EAS AF: 0.000425

Gnomad4 SAS AF: 0.00879

Gnomad4 FIN AF: 0.000244

Gnomad4 NFE AF: 0.00244

Gnomad4 OTH AF: 0.00252

Alfa AF: 0.000867 Hom.: 0

Bravo AF: 0.00131

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

SOX1: BS2; SOX1-OT: BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs764819870; hg19: chr13-112722657;