dbSNP rs7485662: SOX5:c.1771+29G>A (chr12-23543182-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.35

Publications

10 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

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.1771+29G>A	intron	N/A	NP_008871.3
SOX5	NM_001261415.3		c.1741+29G>A	intron	N/A	NP_001248344.1	P35711-5
SOX5	NM_152989.5		c.1732+29G>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.1771+29G>A	intron	N/A	ENSP00000398273.2	P35711-1
SOX5	ENST00000396007.6	TSL:1	c.613+29G>A	intron	N/A	ENSP00000379328.2	P35711-3
SOX5	ENST00000900854.1		c.1771+29G>A	intron	N/A	ENSP00000570913.1

Frequencies

GnomAD3 genomes

AF:

0.511

AC:

77542

AN:

151804

Hom.:

19905

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.510

AC XY:

362031

AN XY:

710144

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

16391

32782

49172

65563

81954

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16068

32136

48204

64272

80340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.511

AC:

77604

AN:

151922

Hom.:

19919

Cov.:

AF XY:

0.510

AC XY:

37891

AN XY:

74232

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1913

3826

5738

7651

9564

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

700

1400

2100

2800

3500

<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:

0.507

Hom.:

13621

Bravo

AF:

0.515

Asia WGS

AF:

0.463

AC:

1609

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Lamb-Shaffer syndrome (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.083

(source)

DANN

Benign

0.66

PhyloP100

-1.4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over