rs760494400

Positions:

• chr18-78994245-G-A
• chr18-78994245-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_171999.4(SALL3):​c.2254G>A​(p.Val752Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,382 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SALL3 NM_171999.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.83

Genes affected

SALL3 (HGNC:10527): (spalt like transcription factor 3) This gene encodes a sal-like C2H2-type zinc-finger protein, and belongs to a family of evolutionarily conserved genes found in species as diverse as Drosophila, C. elegans, and vertebrates. Mutations in some of these genes are associated with congenital disorders in human, suggesting their importance in embryonic development. This protein binds to DNA methyltransferase 3 alpha (DNMT3A), and reduces DNMT3A-mediated CpG island methylation. It is suggested that silencing of this gene, resulting in acceleration of DNA methylation, may have a role in oncogenesis. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 18-78994245-G-A is Benign according to our data. Variant chr18-78994245-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 221917.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL3	NM_171999.4	c.2254G>A	p.Val752Met	missense_variant	2/3	ENST00000537592.7	NP_741996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SALL3	ENST00000537592.7	c.2254G>A	p.Val752Met	missense_variant	2/3	5	NM_171999.4	ENSP00000441823	P1
SALL3	ENST00000575389.6	c.2254G>A	p.Val752Met	missense_variant	2/4	5		ENSP00000458360
SALL3	ENST00000536229.7	c.1855G>A	p.Val619Met	missense_variant	1/3	3		ENSP00000439975

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461382 Hom.: 0 Cov.: 89 AF XY: 0.00000413 AC XY: 3 AN XY: 727006

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000624 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Anophthalmia-microphthalmia syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Paul Sabatier University EA-4555, Paul Sabatier University

Jan 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.089	T;.;T;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.60	D;D;D;D
MetaSVM	Uncertain	0.033	D
MutationAssessor	Benign	1.0	.;L;L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-2.3	.;.;N;.
REVEL	Uncertain	0.46
Sift	Benign	0.051	.;.;T;.
Sift4G	Uncertain	0.040	D;D;D;D
Polyphen		1.0	.;.;D;.
Vest4		0.67
MutPred		0.50		.;Gain of MoRF binding (P = 0.0798);Gain of MoRF binding (P = 0.0798);.;
MVP		0.88
MPC		1.2
ClinPred		0.87	D
GERP RS		5.2
Varity_R		0.17
gMVP		0.39

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: rs760494400; hg19: chr18-76754245; COSMIC: COSV73306376; COSMIC: COSV73306376;