20-51784019-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_020436.5(SALL4):c.*245del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 486,892 control chromosomes in the GnomAD database, including 311 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.031 (89 hom., cov: 31)
  • Exomes 𝑓: 0.032 (222 hom.)
• Consequence: SALL4 NM_020436.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.28

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 -10 ACMG points.

• BP6: Variant 20-51784019-CA-C is Benign according to our data. Variant chr20-51784019-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1190265.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0314 (4689/149192) while in subpopulation SAS AF= 0.054 (255/4724). AF 95% confidence interval is 0.0485. There are 89 homozygotes in gnomad4. There are 2270 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 4686 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SALL4	NM_020436.5	c.*245del		3_prime_UTR_variant	4/4	ENST00000217086.9
SALL4	NM_001318031.2	c.*245del		3_prime_UTR_variant	4/4
SALL4	XM_047440318.1	c.*245del		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SALL4	ENST00000217086.9	c.*245del		3_prime_UTR_variant	4/4	1	NM_020436.5	P1
SALL4	ENST00000371539.7			downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.0314 AC: 4686 AN: 149074 Hom.: 90 Cov.: 31

Gnomad AFR AF: 0.0306

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.0285

Gnomad ASJ AF: 0.0767

Gnomad EAS AF: 0.0514

Gnomad SAS AF: 0.0552

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0279

Gnomad OTH AF: 0.0370

GnomAD4 exome AF: 0.0323 AC: 10910 AN: 337700 Hom.: 222 Cov.: 3 AF XY: 0.0338 AC XY: 6107 AN XY: 180598

Gnomad4 AFR exome AF: 0.0325

Gnomad4 AMR exome AF: 0.0205

Gnomad4 ASJ exome AF: 0.0814

Gnomad4 EAS exome AF: 0.0398

Gnomad4 SAS exome AF: 0.0481

Gnomad4 FIN exome AF: 0.0160

Gnomad4 NFE exome AF: 0.0279

Gnomad4 OTH exome AF: 0.0334

GnomAD4 genome AF: 0.0314 AC: 4689 AN: 149192 Hom.: 89 Cov.: 31 AF XY: 0.0312 AC XY: 2270 AN XY: 72680

Gnomad4 AFR AF: 0.0307

Gnomad4 AMR AF: 0.0285

Gnomad4 ASJ AF: 0.0767

Gnomad4 EAS AF: 0.0515

Gnomad4 SAS AF: 0.0540

Gnomad4 FIN AF: 0.0124

Gnomad4 NFE AF: 0.0279

Gnomad4 OTH AF: 0.0366

Bravo AF: 0.0330

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs60718711; hg19: chr20-50400558;