rs6021435

Variant names:

• chr20-51783541-A-C
• rs6021435
• NM_020436.5:c.*724T>G

Your query was ambiguous. Multiple possible variants found:

• chr20-51783541-A-C
• chr20-51783541-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020436.5(SALL4):​c.*724T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,972 control chromosomes in the GnomAD database, including 10,682 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (10677 hom., cov: 30)
  • Exomes 𝑓: 0.18 (5 hom.)
• Consequence: SALL4 NM_020436.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472
• Publications: 8 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

ENSG00000303179 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 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.*724T>G		3_prime_UTR	Exon 4 of 4	NP_065169.1
	SALL4	NM_001318031.2		c.*724T>G		3_prime_UTR	Exon 4 of 4	NP_001304960.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL4	ENST00000217086.9	TSL:1 MANE Select	c.*724T>G		3_prime_UTR	Exon 4 of 4	ENSP00000217086.4
	ENSG00000303179	ENST00000792520.1		n.231-754A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53096 AN: 151544 Hom.: 10652 Cov.: 30

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.381

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.345

GnomAD4 exome AF: 0.176 AC: 54 AN: 306 Hom.: 5 Cov.: 0 AF XY: 0.190 AC XY: 33 AN XY: 174

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.105 AC: 4 AN: 38

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.250 AC: 1 AN: 4

South Asian (SAS) AF: 0.100 AC: 2 AN: 20

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.191 AC: 45 AN: 236

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.351 AC: 53186 AN: 151666 Hom.: 10677 Cov.: 30 AF XY: 0.351 AC XY: 25971 AN XY: 74084

African (AFR) AF: 0.555 AC: 22942 AN: 41312

American (AMR) AF: 0.296 AC: 4502 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1117 AN: 3460

East Asian (EAS) AF: 0.294 AC: 1515 AN: 5154

South Asian (SAS) AF: 0.265 AC: 1272 AN: 4806

European-Finnish (FIN) AF: 0.293 AC: 3081 AN: 10504

Middle Eastern (MID) AF: 0.386 AC: 112 AN: 290

European-Non Finnish (NFE) AF: 0.259 AC: 17590 AN: 67920

Other (OTH) AF: 0.348 AC: 733 AN: 2106

Alfa AF: 0.270 Hom.: 5276

Bravo AF: 0.359

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.51
PhyloP100		-0.47

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: rs6021435; hg19: chr20-50400080; COSMIC: COSV107248958; COSMIC: COSV107248958;