rs13043248

Variant names:

• chr20-51790446-G-A
• rs13043248
• NM_020436.5:c.2037C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_020436.5(SALL4):​c.2037C>T​(p.Thr679Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0915 in 1,613,982 control chromosomes in the GnomAD database, including 7,417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.072 (539 hom., cov: 32)
  • Exomes 𝑓: 0.093 (6878 hom.)
• Consequence: SALL4 NM_020436.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -7.05
• Publications: 13 publications found

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 20-51790446-G-A is Benign according to our data. Variant chr20-51790446-G-A is described in ClinVar as Benign. ClinVar VariationId is 261261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-7.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL4	NM_020436.5	MANE Select	c.2037C>T	p.Thr679Thr	synonymous	Exon 2 of 4	NP_065169.1
	SALL4	NM_001318031.2		c.1150+887C>T		intron	N/A	NP_001304960.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL4	ENST00000217086.9	TSL:1 MANE Select	c.2037C>T	p.Thr679Thr	synonymous	Exon 2 of 4	ENSP00000217086.4
	SALL4	ENST00000395997.3	TSL:1	c.1150+887C>T		intron	N/A	ENSP00000379319.3
	SALL4	ENST00000371539.7	TSL:1	c.131-1305C>T		intron	N/A	ENSP00000360594.3

Frequencies

GnomAD3 genomes AF: 0.0725 AC: 11024 AN: 152060 Hom.: 540 Cov.: 32

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0699

Gnomad ASJ AF: 0.0807

Gnomad EAS AF: 0.0319

Gnomad SAS AF: 0.0460

Gnomad FIN AF: 0.0838

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0895

GnomAD2 exomes AF: 0.0755 AC: 18971 AN: 251148 AF XY: 0.0769

Gnomad AFR exome AF: 0.0182

Gnomad AMR exome AF: 0.0480

Gnomad ASJ exome AF: 0.0888

Gnomad EAS exome AF: 0.0274

Gnomad FIN exome AF: 0.0901

Gnomad NFE exome AF: 0.104

Gnomad OTH exome AF: 0.0865

GnomAD4 exome AF: 0.0935 AC: 136607 AN: 1461804 Hom.: 6878 Cov.: 34 AF XY: 0.0924 AC XY: 67173 AN XY: 727206

African (AFR) AF: 0.0185 AC: 621 AN: 33480

American (AMR) AF: 0.0490 AC: 2192 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0876 AC: 2289 AN: 26136

East Asian (EAS) AF: 0.0411 AC: 1630 AN: 39700

South Asian (SAS) AF: 0.0456 AC: 3936 AN: 86258

European-Finnish (FIN) AF: 0.0912 AC: 4868 AN: 53350

Middle Eastern (MID) AF: 0.0921 AC: 531 AN: 5768

European-Non Finnish (NFE) AF: 0.103 AC: 115068 AN: 1111996

Other (OTH) AF: 0.0906 AC: 5472 AN: 60394

GnomAD4 genome AF: 0.0724 AC: 11015 AN: 152178 Hom.: 539 Cov.: 32 AF XY: 0.0703 AC XY: 5229 AN XY: 74402

African (AFR) AF: 0.0209 AC: 868 AN: 41544

American (AMR) AF: 0.0698 AC: 1066 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0807 AC: 280 AN: 3468

East Asian (EAS) AF: 0.0320 AC: 165 AN: 5164

South Asian (SAS) AF: 0.0460 AC: 222 AN: 4824

European-Finnish (FIN) AF: 0.0838 AC: 887 AN: 10586

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7209 AN: 67994

Other (OTH) AF: 0.0871 AC: 184 AN: 2112

Alfa AF: 0.0947 Hom.: 1236

Bravo AF: 0.0685

Asia WGS AF: 0.0370 AC: 130 AN: 3478

EpiCase AF: 0.104

EpiControl AF: 0.102

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	1	Duane-radial ray syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.0070
DANN	Benign	0.49
PhyloP100		-7.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13043248; hg19: chr20-50406985; COSMIC: COSV53856687; COSMIC: COSV53856687;