rs6021435

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL4	NM_020436.5	c.*724T>G		3_prime_UTR_variant	4/4	ENST00000217086.9	NP_065169.1
SALL4	NM_001318031.2	c.*724T>G		3_prime_UTR_variant	4/4		NP_001304960.1
SALL4	XM_047440318.1	c.*724T>G		3_prime_UTR_variant	4/4		XP_047296274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SALL4	ENST00000217086	c.*724T>G		3_prime_UTR_variant	4/4	1	NM_020436.5	ENSP00000217086.4

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.105

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.100

Gnomad4 NFE exome AF: 0.191

Gnomad4 OTH exome AF: 0.333

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

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.348

Alfa AF: 0.263 Hom.: 4248

Bravo AF: 0.359

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs6021435; hg19: chr20-50400080;