rs61737142

Positions:

• chr20-51790301-C-G
• chr20-51790301-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020436.5(SALL4):​c.2182G>C​(p.Ala728Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0041 in 1,614,154 control chromosomes in the GnomAD database, including 254 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (139 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (115 hom.)
• Consequence: SALL4 NM_020436.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.630

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027288496).
• BP6: Variant 20-51790301-C-G is Benign according to our data. Variant chr20-51790301-C-G is described in ClinVar as [Benign]. Clinvar id is 287110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL4	NM_020436.5	c.2182G>C	p.Ala728Pro	missense_variant	2/4	ENST00000217086.9	NP_065169.1
SALL4	XM_047440318.1	c.1876G>C	p.Ala626Pro	missense_variant	2/4		XP_047296274.1
SALL4	NM_001318031.2	c.1150+1032G>C		intron_variant			NP_001304960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SALL4	ENST00000217086.9	c.2182G>C	p.Ala728Pro	missense_variant	2/4	1	NM_020436.5	ENSP00000217086.4
SALL4	ENST00000395997.3	c.1150+1032G>C		intron_variant		1		ENSP00000379319.3
SALL4	ENST00000371539.7	c.131-1160G>C		intron_variant		1		ENSP00000360594.3

Frequencies

GnomAD3 genomes AF: 0.0219 AC: 3331 AN: 152154 Hom.: 138 Cov.: 32

Gnomad AFR AF: 0.0763

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00798

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.0148

GnomAD3 exomes AF: 0.00574 AC: 1442 AN: 251352 Hom.: 45 AF XY: 0.00434 AC XY: 590 AN XY: 135870

Gnomad AFR exome AF: 0.0783

Gnomad AMR exome AF: 0.00379

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000220

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00224 AC: 3279 AN: 1461882 Hom.: 115 Cov.: 31 AF XY: 0.00198 AC XY: 1443 AN XY: 727240

Gnomad4 AFR exome AF: 0.0765

Gnomad4 AMR exome AF: 0.00432

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000139

Gnomad4 OTH exome AF: 0.00578

GnomAD4 genome AF: 0.0219 AC: 3341 AN: 152272 Hom.: 139 Cov.: 32 AF XY: 0.0217 AC XY: 1618 AN XY: 74448

Gnomad4 AFR AF: 0.0763

Gnomad4 AMR AF: 0.00797

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000220

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.00320 Hom.: 12

Bravo AF: 0.0249

ESP6500AA AF: 0.0767 AC: 338

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00719 AC: 873

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Apr 08, 2016

- -

Duane-radial ray syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	2.9	M
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.10
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.15	T
Polyphen		0.028	B
Vest4		0.67
MVP		0.20
MPC		0.88
ClinPred		0.046	T
GERP RS		3.6
Varity_R		0.25
gMVP		0.31

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: rs61737142; hg19: chr20-50406840;