12-23543182-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006940.6(SOX5):c.1771+29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 1,579,830 control chromosomes in the GnomAD database, including 207,987 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (19919 hom., cov: 31)
  • Exomes 𝑓: 0.51 (188068 hom.)
• Consequence: SOX5 NM_006940.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.35

Genes affected

SOX5 (HGNC:11201): (SRY-box transcription factor 5) 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 regulator after forming a protein complex with other proteins. The encoded protein may play a role in chondrogenesis. A pseudogene of this gene is located on chromosome 8. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 12-23543182-C-T is Benign according to our data. Variant chr12-23543182-C-T is described in ClinVar as [Benign]. Clinvar id is 1333149.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX5	NM_006940.6	c.1771+29G>A		intron_variant		ENST00000451604.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX5	ENST00000451604.7	c.1771+29G>A		intron_variant		1	NM_006940.6	A1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77542 AN: 151804 Hom.: 19905 Cov.: 31

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.497

GnomAD3 exomes AF: 0.509 AC: 126431 AN: 248148 Hom.: 32615 AF XY: 0.507 AC XY: 68047 AN XY: 134132

Gnomad AFR exome AF: 0.522

Gnomad AMR exome AF: 0.554

Gnomad ASJ exome AF: 0.380

Gnomad EAS exome AF: 0.448

Gnomad SAS exome AF: 0.476

Gnomad FIN exome AF: 0.541

Gnomad NFE exome AF: 0.518

Gnomad OTH exome AF: 0.515

GnomAD4 exome AF: 0.512 AC: 730389 AN: 1427908 Hom.: 188068 Cov.: 23 AF XY: 0.510 AC XY: 362031 AN XY: 710144

Gnomad4 AFR exome AF: 0.520

Gnomad4 AMR exome AF: 0.547

Gnomad4 ASJ exome AF: 0.374

Gnomad4 EAS exome AF: 0.461

Gnomad4 SAS exome AF: 0.471

Gnomad4 FIN exome AF: 0.538

Gnomad4 NFE exome AF: 0.518

Gnomad4 OTH exome AF: 0.490

GnomAD4 genome AF: 0.511 AC: 77604 AN: 151922 Hom.: 19919 Cov.: 31 AF XY: 0.510 AC XY: 37891 AN XY: 74232

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.494

Alfa AF: 0.507 Hom.: 12515

Bravo AF: 0.515

Asia WGS AF: 0.463 AC: 1609 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Lamb-Shaffer syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.083
Dann	Benign	0.66

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: rs7485662; hg19: chr12-23696116;