Variant 20-51791838-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_020436.5(SALL4):c.645C>G(p.Leu215=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0278 in 1,614,128 control chromosomes in the GnomAD database, including 755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 55 hom., cov: 33)

Exomes 𝑓: 0.029 ( 700 hom. )

Consequence

SALL4
NM_020436.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.603

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 20-51791838-G-C is Benign according to our data. Variant chr20-51791838-G-C is described in ClinVar as [Benign]. Clinvar id is 261265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-51791838-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.603 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0206 (3132/152348) while in subpopulation NFE AF= 0.0334 (2272/68034). AF 95% confidence interval is 0.0323. There are 55 homozygotes in gnomad4. There are 1507 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3132 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SALL4	NM_020436.5 linkuse as main transcript	c.645C>G	p.Leu215=	synonymous_variant	2/4	ENST00000217086.9
SALL4	NM_001318031.2 linkuse as main transcript	c.645C>G	p.Leu215=	synonymous_variant	2/4
SALL4	XM_047440318.1 linkuse as main transcript	c.339C>G	p.Leu113=	synonymous_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SALL4	ENST00000217086.9 linkuse as main transcript	c.645C>G	p.Leu215=	synonymous_variant	2/4	1	NM_020436.5	P1	Q9UJQ4-1
SALL4	ENST00000395997.3 linkuse as main transcript	c.645C>G	p.Leu215=	synonymous_variant	2/4	1			Q9UJQ4-2
SALL4	ENST00000371539.7 linkuse as main transcript	c.131-2697C>G		intron_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0206

AC:

3133

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00499

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0133

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0281

Gnomad FIN

AF:

0.0210

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0334

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.0232

AC:

5832

AN:

250948

Hom.:

105

AF XY:

0.0243

AC XY:

3296

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.00427

Gnomad AMR exome

AF:

0.00917

Gnomad ASJ exome

AF:

0.0144

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0268

Gnomad FIN exome

AF:

0.0206

Gnomad NFE exome

AF:

0.0343

Gnomad OTH exome

AF:

0.0228

GnomAD4 exome

AF:

0.0286

AC:

41777

AN:

1461780

Hom.:

700

Cov.:

AF XY:

0.0288

AC XY:

20912

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00397

Gnomad4 AMR exome

AF:

0.00901

Gnomad4 ASJ exome

AF:

0.0163

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0281

Gnomad4 FIN exome

AF:

0.0208

Gnomad4 NFE exome

AF:

0.0320

Gnomad4 OTH exome

AF:

0.0263

GnomAD4 genome

AF:

0.0206

AC:

3132

AN:

152348

Hom.:

Cov.:

AF XY:

0.0202

AC XY:

1507

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00498

Gnomad4 AMR

AF:

0.0133

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0282

Gnomad4 FIN

AF:

0.0210

Gnomad4 NFE

AF:

0.0334

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0223

Hom.:

Bravo

AF:

0.0181

Asia WGS

AF:

0.00837

AC:

AN:

3478

EpiCase

AF:

0.0296

EpiControl

AF:

0.0290

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Duane-radial ray syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.64

DANN

Benign

0.69

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over