Genetic Variant SOX5:c.1165-8554G>A (chr12-23584392-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006940.6(SOX5):c.1165-8554G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,032 control chromosomes in the GnomAD database, including 4,928 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 0.24 ( 4928 hom., cov: 32)

Consequence

SOX5
NM_006940.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.323

Publications

5 publications found

Variant links:

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: G2P, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae)
developmental and speech delay due to SOX5 deficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SOX5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006940.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SOX5	NM_006940.6	MANE Select	c.1165-8554G>A	intron	N/A	NP_008871.3
SOX5	NM_001261415.3		c.1135-8554G>A	intron	N/A	NP_001248344.1	P35711-5
SOX5	NM_152989.5		c.1126-8554G>A	intron	N/A	NP_694534.1	T2CYZ2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SOX5	ENST00000451604.7	TSL:1 MANE Select	c.1165-8554G>A	intron	N/A	ENSP00000398273.2	P35711-1
SOX5	ENST00000396007.6	TSL:1	c.6+155G>A	intron	N/A	ENSP00000379328.2	P35711-3
SOX5	ENST00000900854.1		c.1165-8554G>A	intron	N/A	ENSP00000570913.1

Frequencies

GnomAD3 genomes

AF:

0.238

AC:

36159

AN:

151914

Hom.:

4926

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.489

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.394

Gnomad EAS

AF:

0.313

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.343

Gnomad MID

AF:

0.306

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.250

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

GnomAD4 genome

AF:

0.238

AC:

36199

AN:

152032

Hom.:

4928

Cov.:

AF XY:

0.241

AC XY:

17901

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.109

AC:

4533

AN:

41510

American (AMR)

AF:

0.189

AC:

2889

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.394

AC:

1367

AN:

3472

East Asian (EAS)

AF:

0.314

AC:

1621

AN:

5170

South Asian (SAS)

AF:

0.282

AC:

1357

AN:

4820

European-Finnish (FIN)

AF:

0.343

AC:

3620

AN:

10564

Middle Eastern (MID)

AF:

0.315

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.291

AC:

19735

AN:

67924

Other (OTH)

AF:

0.255

AC:

539

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1382

2764

4145

5527

6909

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

382

764

1146

1528

1910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.271

Hom.:

8337

Bravo

AF:

0.220

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.2

(source)

DANN

Benign

0.42

PhyloP100

0.32

PromoterAI

-0.00060

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over