20-51784019-C-CAA

Variant names:

• chr20-51784019-C-CAA
• rs60718711
• NM_020436.5:c.*244_*245dupTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020436.5(SALL4):​c.*244_*245dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0451 in 487,208 control chromosomes in the GnomAD database, including 301 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.047 (183 hom., cov: 31)
  • Exomes 𝑓: 0.044 (118 hom.)
• Consequence: SALL4 NM_020436.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.28
• Publications: 1 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

ENSG00000303179 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 20-51784019-C-CAA is Benign according to our data. Variant chr20-51784019-C-CAA is described in ClinVar as Benign. ClinVar VariationId is 1233920.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0624 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.*244_*245dupTT		3_prime_UTR	Exon 4 of 4	NP_065169.1	Q9UJQ4-1
	SALL4	NM_001318031.2		c.*244_*245dupTT		3_prime_UTR	Exon 4 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.*244_*245dupTT		3_prime_UTR	Exon 4 of 4	ENSP00000217086.4	Q9UJQ4-1
	ENSG00000303179	ENST00000792520.1		n.231-268_231-267dupAA		intron	N/A
	SALL4	ENST00000395997.3	TSL:1	c.*244_*245dupTT		downstream_gene	N/A	ENSP00000379319.3	Q9UJQ4-2

Frequencies

GnomAD3 genomes AF: 0.0470 AC: 7004 AN: 149008 Hom.: 183 Cov.: 31

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0419

Gnomad ASJ AF: 0.0255

Gnomad EAS AF: 0.0336

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.0591

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0640

Gnomad OTH AF: 0.0532

GnomAD4 exome AF: 0.0443 AC: 14973 AN: 338082 Hom.: 118 Cov.: 3 AF XY: 0.0435 AC XY: 7874 AN XY: 180832

African (AFR) AF: 0.0188 AC: 186 AN: 9906

American (AMR) AF: 0.0308 AC: 459 AN: 14908

Ashkenazi Jewish (ASJ) AF: 0.0253 AC: 254 AN: 10044

East Asian (EAS) AF: 0.0390 AC: 797 AN: 20448

South Asian (SAS) AF: 0.0280 AC: 1163 AN: 41506

European-Finnish (FIN) AF: 0.0471 AC: 813 AN: 17264

Middle Eastern (MID) AF: 0.0176 AC: 25 AN: 1424

European-Non Finnish (NFE) AF: 0.0512 AC: 10431 AN: 203588

Other (OTH) AF: 0.0445 AC: 845 AN: 18994

GnomAD4 genome AF: 0.0470 AC: 7002 AN: 149126 Hom.: 183 Cov.: 31 AF XY: 0.0459 AC XY: 3336 AN XY: 72652

African (AFR) AF: 0.0218 AC: 887 AN: 40696

American (AMR) AF: 0.0418 AC: 628 AN: 15020

Ashkenazi Jewish (ASJ) AF: 0.0255 AC: 88 AN: 3454

East Asian (EAS) AF: 0.0337 AC: 172 AN: 5110

South Asian (SAS) AF: 0.0315 AC: 149 AN: 4724

European-Finnish (FIN) AF: 0.0591 AC: 567 AN: 9600

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0640 AC: 4303 AN: 67254

Other (OTH) AF: 0.0521 AC: 108 AN: 2072

Alfa AF: 0.0201 Hom.: 16

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs60718711; hg19: chr20-50400558; COSMIC: COSV53854114; COSMIC: COSV53854114;