12-23901638-G-T

Variant names:

• chr12-23901638-G-T
• rs7136898
• NM_006940.6:c.39-5614C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006940.6(SOX5):​c.39-5614C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,832 control chromosomes in the GnomAD database, including 9,455 homozygotes. 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: 𝑓 0.33 (9455 hom., cov: 32)
• Consequence: SOX5 NM_006940.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX5	NM_006940.6	c.39-5614C>A		intron_variant	Intron 1 of 14	ENST00000451604.7	NP_008871.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX5	ENST00000451604.7	c.39-5614C>A		intron_variant	Intron 1 of 14	1	NM_006940.6	ENSP00000398273.2

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49954 AN: 151714 Hom.: 9455 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.0865

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.320

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.329 AC: 49950 AN: 151832 Hom.: 9455 Cov.: 32 AF XY: 0.324 AC XY: 24007 AN XY: 74182

African (AFR) AF: 0.170 AC: 7050 AN: 41390

American (AMR) AF: 0.250 AC: 3819 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1345 AN: 3466

East Asian (EAS) AF: 0.0858 AC: 443 AN: 5166

South Asian (SAS) AF: 0.295 AC: 1419 AN: 4812

European-Finnish (FIN) AF: 0.435 AC: 4574 AN: 10504

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30053 AN: 67922

Other (OTH) AF: 0.317 AC: 670 AN: 2114

Alfa AF: 0.397 Hom.: 22672

Bravo AF: 0.308

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.63
DANN	Benign	0.78
PhyloP100		0.055
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7136898; hg19: chr12-24054572;