20-51784053-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020436.5(SALL4):c.*211_*212insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0599 in 538,912 control chromosomes in the GnomAD database, including 422 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.055 (225 hom., cov: 31)
  • Exomes 𝑓: 0.062 (197 hom.)
• Consequence: SALL4 NM_020436.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.445

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 20-51784053-A-AT is Benign according to our data. Variant chr20-51784053-A-AT is described in ClinVar as [Benign]. Clinvar id is 1296361.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SALL4	NM_020436.5	c.*211_*212insA		3_prime_UTR_variant	4/4	ENST00000217086.9
SALL4	NM_001318031.2	c.*211_*212insA		3_prime_UTR_variant	4/4
SALL4	XM_047440318.1	c.*211_*212insA		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SALL4	ENST00000217086.9	c.*211_*212insA		3_prime_UTR_variant	4/4	1	NM_020436.5	P1
SALL4	ENST00000371539.7	c.*211_*212insA		3_prime_UTR_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.0545 AC: 8176 AN: 150068 Hom.: 222 Cov.: 31

Gnomad AFR AF: 0.0460

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0455

Gnomad ASJ AF: 0.0308

Gnomad EAS AF: 0.0341

Gnomad SAS AF: 0.0321

Gnomad FIN AF: 0.0571

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.0648

Gnomad OTH AF: 0.0599

GnomAD4 exome AF: 0.0620 AC: 24114 AN: 388748 Hom.: 197 Cov.: 4 AF XY: 0.0607 AC XY: 12495 AN XY: 205876

Gnomad4 AFR exome AF: 0.0524

Gnomad4 AMR exome AF: 0.0424

Gnomad4 ASJ exome AF: 0.0427

Gnomad4 EAS exome AF: 0.0617

Gnomad4 SAS exome AF: 0.0347

Gnomad4 FIN exome AF: 0.0657

Gnomad4 NFE exome AF: 0.0689

Gnomad4 OTH exome AF: 0.0621

GnomAD4 genome AF: 0.0545 AC: 8188 AN: 150164 Hom.: 225 Cov.: 31 AF XY: 0.0533 AC XY: 3902 AN XY: 73270

Gnomad4 AFR AF: 0.0460

Gnomad4 AMR AF: 0.0454

Gnomad4 ASJ AF: 0.0308

Gnomad4 EAS AF: 0.0342

Gnomad4 SAS AF: 0.0322

Gnomad4 FIN AF: 0.0571

Gnomad4 NFE AF: 0.0648

Gnomad4 OTH AF: 0.0646

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 09, 2019

- -

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: rs59841639; hg19: chr20-50400592;