20-51790353-C-T

Variant names:

Variant summary

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

The NM_020436.5(SALL4):c.2130G>A(p.Thr710Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00308 in 1,614,048 control chromosomes in the GnomAD database, including 148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 84 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 64 hom. )

Consequence

SALL4
NM_020436.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.69

Publications

2 publications found

Variant links:

Genes affected

SALL4 (HGNC:15924): (spalt like transcription factor 4) This gene encodes a zinc finger transcription factor thought to play a role in the development of abducens motor neurons. Defects in this gene are a cause of Duane-radial ray syndrome (DRRS). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

SALL4 Gene-Disease associations (from GenCC):

Duane-radial ray syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
Duane retraction syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
IVIC syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SALL4 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=-0.81).

BP6

Variant 20-51790353-C-T is Benign according to our data. Variant chr20-51790353-C-T is described in ClinVar as Benign. ClinVar VariationId is 338772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL4	NM_020436.5 link	c.2130G>A	p.Thr710Thr	synonymous_variant	Exon 2 of 4	ENST00000217086.9	NP_065169.1	Q9UJQ4-1
SALL4	XM_047440318.1 link	c.1824G>A	p.Thr608Thr	synonymous_variant	Exon 2 of 4		XP_047296274.1
SALL4	NM_001318031.2 link	c.1150+980G>A		intron_variant	Intron 2 of 3		NP_001304960.1	Q9UJQ4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SALL4	ENST00000217086.9 link	c.2130G>A	p.Thr710Thr	synonymous_variant	Exon 2 of 4	1	NM_020436.5	ENSP00000217086.4	Q9UJQ4-1
SALL4	ENST00000395997.3 link	c.1150+980G>A		intron_variant	Intron 2 of 3	1		ENSP00000379319.3	Q9UJQ4-2
SALL4	ENST00000371539.7 link	c.131-1212G>A		intron_variant	Intron 1 of 2	1		ENSP00000360594.3	Q6Y8G5

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2484

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0572

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00518

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00912

GnomAD2 exomes

AF:

0.00424

AC:

1066

AN:

251230

AF XY:

0.00324

show subpopulations

Gnomad AFR exome

AF:

0.0577

Gnomad AMR exome

AF:

0.00289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00170

AC:

2482

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

1099

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.0572

AC:

1916

AN:

33478

American (AMR)

AF:

0.00320

AC:

143

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000139

AC:

155

AN:

1112012

Other (OTH)

AF:

0.00414

AC:

250

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

175

350

525

700

875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<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:

0.0164

AC:

2491

AN:

152198

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1200

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0572

AC:

2376

AN:

41530

American (AMR)

AF:

0.00517

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

68006

Other (OTH)

AF:

0.00950

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

124

249

373

498

622

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00583

Hom.:

Bravo

AF:

0.0184

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Duane-radial ray syndrome

Benign:1

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oculootoradial syndrome;C1623209:Duane-radial ray syndrome

Benign:1

Jul 18, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.20

(source)

DANN

Benign

0.36

PhyloP100

-1.7

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over