20-51784292-C-A

Variant names:

• chr20-51784292-C-A
• NM_020436.5:c.3135G>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_020436.5(SALL4):​c.3135G>T​(p.Leu1045Leu) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SALL4 NM_020436.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.916

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=-0.41).
• BP6: Variant 20-51784292-C-A is Benign according to our data. Variant chr20-51784292-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3657420.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.916 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL4	NM_020436.5	c.3135G>T	p.Leu1045Leu	synonymous_variant	Exon 4 of 4	ENST00000217086.9	NP_065169.1
SALL4	NM_001318031.2	c.1824G>T	p.Leu608Leu	synonymous_variant	Exon 4 of 4		NP_001304960.1
SALL4	XM_047440318.1	c.2829G>T	p.Leu943Leu	synonymous_variant	Exon 4 of 4		XP_047296274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SALL4	ENST00000217086.9	c.3135G>T	p.Leu1045Leu	synonymous_variant	Exon 4 of 4	1	NM_020436.5	ENSP00000217086.4
SALL4	ENST00000395997.3	c.1824G>T	p.Leu608Leu	synonymous_variant	Exon 4 of 4	1		ENSP00000379319.3
SALL4	ENST00000371539.7	c.804G>T	p.Leu268Leu	synonymous_variant	Exon 3 of 3	1		ENSP00000360594.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Duane-radial ray syndrome Benign:1

Sep 27, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	8.1
DANN	Benign	0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-50400831;