chr20-51784266-T-C

Position:

• chr20-51784266-T-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The ENST00000395997.3(SALL4):​c.1850A>G​(p.Ter617Ter) variant causes a splice region, stop retained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SALL4 ENST00000395997.3 splice_region, stop_retained
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.633

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=0.633 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL4	NM_020436.5	c.3161A>G	p.Ter1054Ter	stop_retained_variant	4/4	ENST00000217086.9	NP_065169.1
SALL4	NM_001318031.2	c.1850A>G	p.Ter617Ter	stop_retained_variant	4/4		NP_001304960.1
SALL4	XM_047440318.1	c.2855A>G	p.Ter952Ter	stop_retained_variant	4/4		XP_047296274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SALL4	ENST00000217086.9	c.3161A>G	p.Ter1054Ter	stop_retained_variant	4/4	1	NM_020436.5	ENSP00000217086.4
SALL4	ENST00000395997.3	c.1850A>G	p.Ter617Ter	splice_region_variant, stop_retained_variant	4/4	1		ENSP00000379319.3
SALL4	ENST00000371539.7	c.830A>G	p.Ter277Ter	stop_retained_variant	3/3	1		ENSP00000360594.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Nov 11, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.4
DANN	Benign	0.60

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: rs1555848961; hg19: chr20-50400805;