chr20-51784019-CA-C

Variant names:

• chr20-51784019-CA-C
• rs60718711
• NM_020436.5:c.*245delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_020436.5(SALL4):​c.*245delT 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
• Publications: 1 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4689 AD gene.

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.*245delT		3_prime_UTR	Exon 4 of 4	NP_065169.1	Q9UJQ4-1
	SALL4	NM_001318031.2		c.*245delT		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.*245delT		3_prime_UTR	Exon 4 of 4	ENSP00000217086.4	Q9UJQ4-1
	ENSG00000303179	ENST00000792520.1		n.231-267delA		intron	N/A
	SALL4	ENST00000395997.3	TSL:1	c.*245delT		downstream_gene	N/A	ENSP00000379319.3	Q9UJQ4-2

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

African (AFR) AF: 0.0325 AC: 321 AN: 9866

American (AMR) AF: 0.0205 AC: 305 AN: 14876

Ashkenazi Jewish (ASJ) AF: 0.0814 AC: 816 AN: 10022

East Asian (EAS) AF: 0.0398 AC: 813 AN: 20402

South Asian (SAS) AF: 0.0481 AC: 1993 AN: 41460

European-Finnish (FIN) AF: 0.0160 AC: 276 AN: 17250

Middle Eastern (MID) AF: 0.0466 AC: 66 AN: 1416

European-Non Finnish (NFE) AF: 0.0279 AC: 5686 AN: 203454

Other (OTH) AF: 0.0334 AC: 634 AN: 18954

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

African (AFR) AF: 0.0307 AC: 1250 AN: 40716

American (AMR) AF: 0.0285 AC: 428 AN: 15022

Ashkenazi Jewish (ASJ) AF: 0.0767 AC: 265 AN: 3454

East Asian (EAS) AF: 0.0515 AC: 263 AN: 5108

South Asian (SAS) AF: 0.0540 AC: 255 AN: 4724

European-Finnish (FIN) AF: 0.0124 AC: 119 AN: 9618

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0279 AC: 1874 AN: 67280

Other (OTH) AF: 0.0366 AC: 76 AN: 2074

Alfa AF: 0.00408 Hom.: 16

Bravo AF: 0.0330

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

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

Other links and lift over

dbSNP: rs60718711; hg19: chr20-50400558;