rs771517621

Variant names:

• chr18-78980319-C-G
• rs771517621
• NM_171999.4:c.45C>G

Your query was ambiguous. Multiple possible variants found:

• chr18-78980319-C-G
• chr18-78980319-C-A
• chr18-78980319-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_171999.4(SALL3):​c.45C>G​(p.Asp15Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000368 in 1,439,074 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000040 (1 hom.)
• Consequence: SALL3 NM_171999.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.79
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018754303).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_171999.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL3	NM_171999.4	MANE Select	c.45C>G	p.Asp15Glu	missense	Exon 1 of 3	NP_741996.2	Q9BXA9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL3	ENST00000537592.7	TSL:5 MANE Select	c.45C>G	p.Asp15Glu	missense	Exon 1 of 3	ENSP00000441823.2	Q9BXA9-1
	SALL3	ENST00000575389.6	TSL:5	c.45C>G	p.Asp15Glu	missense	Exon 1 of 4	ENSP00000458360.2	Q9BXA9-2
	SALL3	ENST00000925065.1		c.45C>G	p.Asp15Glu	missense	Exon 1 of 3	ENSP00000595124.1

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151320 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000245 AC: 21 AN: 85754 AF XY: 0.000268

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000396

GnomAD4 exome AF: 0.0000404 AC: 52 AN: 1287754 Hom.: 1 Cov.: 30 AF XY: 0.0000567 AC XY: 36 AN XY: 634668

African (AFR) AF: 0.00 AC: 0 AN: 26104

American (AMR) AF: 0.00 AC: 0 AN: 27870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22116

East Asian (EAS) AF: 0.00 AC: 0 AN: 27188

South Asian (SAS) AF: 0.000621 AC: 44 AN: 70860

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35360

Middle Eastern (MID) AF: 0.000271 AC: 1 AN: 3694

European-Non Finnish (NFE) AF: 0.00000196 AC: 2 AN: 1022526

Other (OTH) AF: 0.0000961 AC: 5 AN: 52036

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151320 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 73916

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41324

American (AMR) AF: 0.00 AC: 0 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5082

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67822

Other (OTH) AF: 0.00 AC: 0 AN: 2074

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000230 AC: 11

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.8
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.047
Sift	Benign	0.70	T
Sift4G	Benign	0.66	T
Polyphen		0.057	B
Vest4		0.12
MutPred		0.16		Gain of helix (P = 0.0199)
MVP		0.31
MPC		0.37
ClinPred		0.039	T
GERP RS		0.73
PromoterAI		-0.064	Neutral
Varity_R		0.091
gMVP		0.082
Mutation Taster		=95/5	polymorphism

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: rs771517621; hg19: chr18-76740319;