20-51784140-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020436.5(SALL4):c.*125T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.057 in 1,149,286 control chromosomes in the GnomAD database, including 2,120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (317 hom., cov: 32)
  • Exomes 𝑓: 0.056 (1803 hom.)
• Consequence: SALL4 NM_020436.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.30

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 20-51784140-A-T is Benign according to our data. Variant chr20-51784140-A-T is described in ClinVar as [Benign]. Clinvar id is 1278396.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SALL4	NM_020436.5	c.*125T>A		3_prime_UTR_variant	4/4	ENST00000217086.9
SALL4	NM_001318031.2	c.*125T>A		3_prime_UTR_variant	4/4
SALL4	XM_047440318.1	c.*125T>A		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SALL4	ENST00000217086.9	c.*125T>A		3_prime_UTR_variant	4/4	1	NM_020436.5	P1
SALL4	ENST00000371539.7	c.*125T>A		3_prime_UTR_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.0606 AC: 9216 AN: 152164 Hom.: 315 Cov.: 32

Gnomad AFR AF: 0.0656

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.0456

Gnomad ASJ AF: 0.0979

Gnomad EAS AF: 0.0508

Gnomad SAS AF: 0.0827

Gnomad FIN AF: 0.0327

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0611

Gnomad OTH AF: 0.0587

GnomAD4 exome AF: 0.0564 AC: 56266 AN: 997004 Hom.: 1803 Cov.: 13 AF XY: 0.0577 AC XY: 29504 AN XY: 511522

Gnomad4 AFR exome AF: 0.0637

Gnomad4 AMR exome AF: 0.0281

Gnomad4 ASJ exome AF: 0.106

Gnomad4 EAS exome AF: 0.0384

Gnomad4 SAS exome AF: 0.0755

Gnomad4 FIN exome AF: 0.0351

Gnomad4 NFE exome AF: 0.0561

Gnomad4 OTH exome AF: 0.0590

GnomAD4 genome AF: 0.0606 AC: 9234 AN: 152282 Hom.: 317 Cov.: 32 AF XY: 0.0600 AC XY: 4469 AN XY: 74460

Gnomad4 AFR AF: 0.0657

Gnomad4 AMR AF: 0.0455

Gnomad4 ASJ AF: 0.0979

Gnomad4 EAS AF: 0.0509

Gnomad4 SAS AF: 0.0816

Gnomad4 FIN AF: 0.0327

Gnomad4 NFE AF: 0.0611

Gnomad4 OTH AF: 0.0638

Alfa AF: 0.0600 Hom.: 30

Bravo AF: 0.0606

Asia WGS AF: 0.0710 AC: 249 AN: 3478

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

Mar 03, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.9
Dann	Benign	0.78

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: rs3171177; hg19: chr20-50400679;