rs6021437

Variant names:

• chr20-51790623-T-A
• rs6021437
• NM_020436.5:c.1860A>T

Your query was ambiguous. Multiple possible variants found:

• chr20-51790623-T-A
• chr20-51790623-T-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_020436.5(SALL4):​c.1860A>T​(p.Thr620Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T620T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SALL4 NM_020436.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• Publications: 24 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• Duane retraction syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• IVIC syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-1.84 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL4	NM_020436.5	c.1860A>T	p.Thr620Thr	synonymous_variant	Exon 2 of 4	ENST00000217086.9	NP_065169.1
SALL4	XM_047440318.1	c.1554A>T	p.Thr518Thr	synonymous_variant	Exon 2 of 4		XP_047296274.1
SALL4	NM_001318031.2	c.1150+710A>T		intron_variant	Intron 2 of 3		NP_001304960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SALL4	ENST00000217086.9	c.1860A>T	p.Thr620Thr	synonymous_variant	Exon 2 of 4	1	NM_020436.5	ENSP00000217086.4
SALL4	ENST00000395997.3	c.1150+710A>T		intron_variant	Intron 2 of 3	1		ENSP00000379319.3
SALL4	ENST00000371539.7	c.131-1482A>T		intron_variant	Intron 1 of 2	1		ENSP00000360594.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 75

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 4479

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.030
DANN	Benign	0.41
PhyloP100		-1.8

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: rs6021437; hg19: chr20-50407162; COSMIC: COSV53854250; COSMIC: COSV53854250;