20-51790623-T-C

Variant names:

• chr20-51790623-T-C
• rs6021437
• NM_020436.5:c.1860A>G

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.1860A>G​(p.Thr620Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 1,613,806 control chromosomes in the GnomAD database, including 101,222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8331 hom., cov: 32)
  • Exomes 𝑓: 0.35 (92891 hom.)
• Consequence: SALL4 NM_020436.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -1.84
• Publications: 24 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=-0.87).
• BP6: Variant 20-51790623-T-C is Benign according to our data. Variant chr20-51790623-T-C is described in ClinVar as Benign. ClinVar VariationId is 261260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.84 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 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.1860A>G	p.Thr620Thr	synonymous	Exon 2 of 4	NP_065169.1
	SALL4	NM_001318031.2		c.1150+710A>G		intron	N/A	NP_001304960.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL4	ENST00000217086.9	TSL:1 MANE Select	c.1860A>G	p.Thr620Thr	synonymous	Exon 2 of 4	ENSP00000217086.4
	SALL4	ENST00000395997.3	TSL:1	c.1150+710A>G		intron	N/A	ENSP00000379319.3
	SALL4	ENST00000371539.7	TSL:1	c.131-1482A>G		intron	N/A	ENSP00000360594.3

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48852 AN: 151872 Hom.: 8341 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.377

GnomAD2 exomes AF: 0.357 AC: 89799 AN: 251362 AF XY: 0.364

Gnomad AFR exome AF: 0.208

Gnomad AMR exome AF: 0.292

Gnomad ASJ exome AF: 0.412

Gnomad EAS exome AF: 0.600

Gnomad FIN exome AF: 0.317

Gnomad NFE exome AF: 0.345

Gnomad OTH exome AF: 0.363

GnomAD4 exome AF: 0.353 AC: 515945 AN: 1461818 Hom.: 92891 Cov.: 75 AF XY: 0.355 AC XY: 258514 AN XY: 727208

African (AFR) AF: 0.207 AC: 6933 AN: 33480

American (AMR) AF: 0.296 AC: 13244 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 10804 AN: 26136

East Asian (EAS) AF: 0.546 AC: 21693 AN: 39700

South Asian (SAS) AF: 0.408 AC: 35208 AN: 86258

European-Finnish (FIN) AF: 0.321 AC: 17137 AN: 53398

Middle Eastern (MID) AF: 0.343 AC: 1976 AN: 5768

European-Non Finnish (NFE) AF: 0.348 AC: 387049 AN: 1111962

Other (OTH) AF: 0.363 AC: 21901 AN: 60394

GnomAD4 genome AF: 0.321 AC: 48852 AN: 151988 Hom.: 8331 Cov.: 32 AF XY: 0.324 AC XY: 24086 AN XY: 74294

African (AFR) AF: 0.217 AC: 8990 AN: 41476

American (AMR) AF: 0.350 AC: 5339 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1473 AN: 3466

East Asian (EAS) AF: 0.587 AC: 3019 AN: 5144

South Asian (SAS) AF: 0.433 AC: 2087 AN: 4816

European-Finnish (FIN) AF: 0.317 AC: 3344 AN: 10550

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23390 AN: 67966

Other (OTH) AF: 0.374 AC: 788 AN: 2106

Alfa AF: 0.325 Hom.: 4479

Bravo AF: 0.321

Asia WGS AF: 0.510 AC: 1772 AN: 3478

EpiCase AF: 0.357

EpiControl AF: 0.362

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	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	-0.87
CADD	Benign	0.037
DANN	Benign	0.34
PhyloP100		-1.8
Mutation Taster		=99/1	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: rs6021437; hg19: chr20-50407162; COSMIC: COSV53851571; COSMIC: COSV53851571;