12-23543182-C-T

Variant names:

• chr12-23543182-C-T
• rs7485662
• NM_006940.6:c.1771+29G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.35
• Publications: 10 publications found

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]

SOX5 Gene-Disease associations (from GenCC):

• Lamb-Shaffer syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• developmental and speech delay due to SOX5 deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1333149.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
SOX5	NM_006940.6	c.1771+29G>A		intron_variant	Intron 13 of 14	ENST00000451604.7	NP_008871.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX5	ENST00000451604.7	c.1771+29G>A		intron_variant	Intron 13 of 14	1	NM_006940.6	ENSP00000398273.2

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

GnomAD2 exomes AF: 0.509 AC: 126431 AN: 248148 AF XY: 0.507

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 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

African (AFR) AF: 0.520 AC: 17057 AN: 32826

American (AMR) AF: 0.547 AC: 24226 AN: 44268

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 9543 AN: 25516

East Asian (EAS) AF: 0.461 AC: 18153 AN: 39380

South Asian (SAS) AF: 0.471 AC: 39799 AN: 84586

European-Finnish (FIN) AF: 0.538 AC: 28532 AN: 53000

Middle Eastern (MID) AF: 0.493 AC: 2799 AN: 5680

European-Non Finnish (NFE) AF: 0.518 AC: 561350 AN: 1083574

Other (OTH) AF: 0.490 AC: 28930 AN: 59078

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

African (AFR) AF: 0.528 AC: 21872 AN: 41428

American (AMR) AF: 0.502 AC: 7667 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1267 AN: 3468

East Asian (EAS) AF: 0.447 AC: 2297 AN: 5144

South Asian (SAS) AF: 0.488 AC: 2349 AN: 4810

European-Finnish (FIN) AF: 0.540 AC: 5699 AN: 10552

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35027 AN: 67930

Other (OTH) AF: 0.494 AC: 1041 AN: 2108

Alfa AF: 0.507 Hom.: 13621

Bravo AF: 0.515

Asia WGS AF: 0.463 AC: 1609 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Lamb-Shaffer syndrome Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.083
DANN	Benign	0.66
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7485662; hg19: chr12-23696116;