20-51784140-A-T

Variant names:

• chr20-51784140-A-T
• rs3171177
• NM_020436.5:c.*125T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.30
• Publications: 7 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, G2P
• 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 -20 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 VariationId is 1278396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0749 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL4	NM_020436.5	MANE Select	c.*125T>A		3_prime_UTR	Exon 4 of 4	NP_065169.1	Q9UJQ4-1
	SALL4	NM_001318031.2		c.*125T>A		3_prime_UTR	Exon 4 of 4	NP_001304960.1	Q9UJQ4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL4	ENST00000217086.9	TSL:1 MANE Select	c.*125T>A		3_prime_UTR	Exon 4 of 4	ENSP00000217086.4	Q9UJQ4-1
	SALL4	ENST00000371539.7	TSL:1	c.*125T>A		3_prime_UTR	Exon 3 of 3	ENSP00000360594.3	Q6Y8G5
	ENSG00000303179	ENST00000792520.1		n.231-155A>T		intron	N/A

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

African (AFR) AF: 0.0637 AC: 1553 AN: 24368

American (AMR) AF: 0.0281 AC: 1107 AN: 39326

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 2387 AN: 22584

East Asian (EAS) AF: 0.0384 AC: 1414 AN: 36794

South Asian (SAS) AF: 0.0755 AC: 5542 AN: 73426

European-Finnish (FIN) AF: 0.0351 AC: 1383 AN: 39414

Middle Eastern (MID) AF: 0.0682 AC: 226 AN: 3314

European-Non Finnish (NFE) AF: 0.0561 AC: 39988 AN: 712562

Other (OTH) AF: 0.0590 AC: 2666 AN: 45216

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

African (AFR) AF: 0.0657 AC: 2731 AN: 41544

American (AMR) AF: 0.0455 AC: 696 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0979 AC: 340 AN: 3472

East Asian (EAS) AF: 0.0509 AC: 264 AN: 5188

South Asian (SAS) AF: 0.0816 AC: 394 AN: 4830

European-Finnish (FIN) AF: 0.0327 AC: 347 AN: 10616

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0611 AC: 4158 AN: 68018

Other (OTH) AF: 0.0638 AC: 135 AN: 2116

Alfa AF: 0.0600 Hom.: 30

Bravo AF: 0.0606

Asia WGS AF: 0.0710 AC: 249 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.78
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs3171177; hg19: chr20-50400679;