NM_020436.5:c.540T>A

Variant names:

• chr20-51791943-A-T
• rs6013281
• NM_020436.5:c.540T>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020436.5(SALL4):​c.540T>A​(p.Asn180Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. N180N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SALL4 NM_020436.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.75

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL4	NM_020436.5	c.540T>A	p.Asn180Lys	missense_variant	Exon 2 of 4	ENST00000217086.9	NP_065169.1
SALL4	NM_001318031.2	c.540T>A	p.Asn180Lys	missense_variant	Exon 2 of 4		NP_001304960.1
SALL4	XM_047440318.1	c.234T>A	p.Asn78Lys	missense_variant	Exon 2 of 4		XP_047296274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SALL4	ENST00000217086.9	c.540T>A	p.Asn180Lys	missense_variant	Exon 2 of 4	1	NM_020436.5	ENSP00000217086.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 93

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.80	D;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.83	T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.75	D;D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Pathogenic	3.1	M;M
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-4.4	D;N
REVEL	Uncertain	0.44
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.020	D;T
Polyphen		1.0	D;.
Vest4		0.88
MutPred		0.54		Gain of MoRF binding (P = 0.0355);Gain of MoRF binding (P = 0.0355);
MVP		0.84
MPC		1.2
ClinPred		1.0	D
GERP RS		-5.0
Varity_R		0.80
gMVP		0.28

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: rs6013281; hg19: chr20-50408482;