20-51791427-C-T

Variant names:

• chr20-51791427-C-T
• rs13038893
• NM_020436.5:c.1056G>A

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.1056G>A​(p.Ala352Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,613,838 control chromosomes in the GnomAD database, including 74,714 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A352A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.29 (6845 hom., cov: 32)
  • Exomes 𝑓: 0.30 (67869 hom.)
• Consequence: SALL4 NM_020436.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.99
• Publications: 17 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: 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 20-51791427-C-T is Benign according to our data. Variant chr20-51791427-C-T is described in ClinVar as Benign. ClinVar VariationId is 261258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.99 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.325 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL4	NM_020436.5	MANE Select	c.1056G>A	p.Ala352Ala	synonymous	Exon 2 of 4	NP_065169.1	Q9UJQ4-1
	SALL4	NM_001318031.2		c.1056G>A	p.Ala352Ala	synonymous	Exon 2 of 4	NP_001304960.1	Q9UJQ4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL4	ENST00000217086.9	TSL:1 MANE Select	c.1056G>A	p.Ala352Ala	synonymous	Exon 2 of 4	ENSP00000217086.4	Q9UJQ4-1
	SALL4	ENST00000395997.3	TSL:1	c.1056G>A	p.Ala352Ala	synonymous	Exon 2 of 4	ENSP00000379319.3	Q9UJQ4-2
	SALL4	ENST00000371539.7	TSL:1	c.131-2286G>A		intron	N/A	ENSP00000360594.3	Q6Y8G5

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44427 AN: 151874 Hom.: 6837 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.0351

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.267

GnomAD2 exomes AF: 0.247 AC: 62002 AN: 251122 AF XY: 0.247

Gnomad AFR exome AF: 0.331

Gnomad AMR exome AF: 0.142

Gnomad ASJ exome AF: 0.230

Gnomad EAS exome AF: 0.0298

Gnomad FIN exome AF: 0.245

Gnomad NFE exome AF: 0.324

Gnomad OTH exome AF: 0.257

GnomAD4 exome AF: 0.298 AC: 435246 AN: 1461844 Hom.: 67869 Cov.: 83 AF XY: 0.294 AC XY: 213750 AN XY: 727220

African (AFR) AF: 0.327 AC: 10948 AN: 33480

American (AMR) AF: 0.150 AC: 6704 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 5991 AN: 26136

East Asian (EAS) AF: 0.0424 AC: 1683 AN: 39700

South Asian (SAS) AF: 0.176 AC: 15183 AN: 86256

European-Finnish (FIN) AF: 0.247 AC: 13190 AN: 53406

Middle Eastern (MID) AF: 0.252 AC: 1453 AN: 5768

European-Non Finnish (NFE) AF: 0.326 AC: 362830 AN: 1111984

Other (OTH) AF: 0.286 AC: 17264 AN: 60390

GnomAD4 genome AF: 0.293 AC: 44462 AN: 151994 Hom.: 6845 Cov.: 32 AF XY: 0.284 AC XY: 21110 AN XY: 74286

African (AFR) AF: 0.325 AC: 13474 AN: 41434

American (AMR) AF: 0.223 AC: 3401 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 760 AN: 3468

East Asian (EAS) AF: 0.0352 AC: 182 AN: 5172

South Asian (SAS) AF: 0.169 AC: 814 AN: 4806

European-Finnish (FIN) AF: 0.242 AC: 2556 AN: 10580

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22335 AN: 67952

Other (OTH) AF: 0.268 AC: 565 AN: 2106

Alfa AF: 0.307 Hom.: 3274

Bravo AF: 0.290

Asia WGS AF: 0.112 AC: 389 AN: 3478

EpiCase AF: 0.321

EpiControl AF: 0.313

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.76
DANN	Benign	0.70
PhyloP100		-2.0
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: rs13038893; hg19: chr20-50407966; COSMIC: COSV53856696; COSMIC: COSV53856696;