Genetic Variant SALL4:c.*245dupT (chr20-51784019-C-CA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_020436.5(SALL4):c.*245dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 486,384 control chromosomes in the GnomAD database, including 8 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0041 ( 8 hom., cov: 31)

Exomes 𝑓: 0.0022 ( 0 hom. )

Consequence

SALL4
NM_020436.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.28

Publications

1 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, G2P
Duane retraction syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
IVIC syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SALL4 links:

ENSG00000303179 (HGNC:):

ENSG00000303179 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 605 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020436.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL4	NM_020436.5	MANE Select	c.*245dupT		3_prime_UTR	Exon 4 of 4	NP_065169.1	Q9UJQ4-1
	SALL4	NM_001318031.2		c.*245dupT		3_prime_UTR	Exon 4 of 4	NP_001304960.1	Q9UJQ4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SALL4	ENST00000217086.9	TSL:1 MANE Select	c.*245dupT	3_prime_UTR	Exon 4 of 4	ENSP00000217086.4	Q9UJQ4-1
ENSG00000303179	ENST00000792520.1		n.231-267dupA	intron	N/A
SALL4	ENST00000395997.3	TSL:1	c.*245dupT	downstream_gene	N/A	ENSP00000379319.3	Q9UJQ4-2

Frequencies

GnomAD3 genomes

AF:

0.00397

AC:

592

AN:

149080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00253

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.000212

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000163

Gnomad OTH

AF:

0.00341

GnomAD4 exome

AF:

0.00217

AC:

732

AN:

337186

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

339

AN XY:

180380

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0158

AC:

156

AN:

9862

American (AMR)

AF:

0.00209

AC:

AN:

14860

Ashkenazi Jewish (ASJ)

AF:

0.00130

AC:

AN:

9988

East Asian (EAS)

AF:

0.00191

AC:

AN:

20402

South Asian (SAS)

AF:

0.000434

AC:

AN:

41432

European-Finnish (FIN)

AF:

0.00186

AC:

AN:

17202

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1418

European-Non Finnish (NFE)

AF:

0.00192

AC:

389

AN:

203092

Other (OTH)

AF:

0.00285

AC:

AN:

18930

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.318

Heterozygous variant carriers

155

232

310

387

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00406

AC:

605

AN:

149198

Hom.:

Cov.:

AF XY:

0.00409

AC XY:

297

AN XY:

72686

show subpopulations

African (AFR)

AF:

0.0131

AC:

534

AN:

40714

American (AMR)

AF:

0.00253

AC:

AN:

15024

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.000196

AC:

AN:

5110

South Asian (SAS)

AF:

0.000212

AC:

AN:

4724

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000163

AC:

AN:

67282

Other (OTH)

AF:

0.00916

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

114

143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

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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20-51784019-CAAAA-CAAAAA

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