Genetic Variant NM_020436.5:c.*724T>G (chr20-51783541-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020436.5(SALL4):c.*724T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,972 control chromosomes in the GnomAD database, including 10,682 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.35 ( 10677 hom., cov: 30)

Exomes 𝑓: 0.18 ( 5 hom. )

Consequence

SALL4
NM_020436.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.472

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

Duane-radial ray syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, G2P
Duane retraction syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
IVIC syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SALL4 links:

ENSG00000303179 (HGNC:):

ENSG00000303179 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020436.5. 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
	SALL4	NM_020436.5	MANE Select	c.*724T>G		3_prime_UTR	Exon 4 of 4	NP_065169.1	Q9UJQ4-1
	SALL4	NM_001318031.2		c.*724T>G		3_prime_UTR	Exon 4 of 4	NP_001304960.1	Q9UJQ4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL4	ENST00000217086.9	TSL:1 MANE Select	c.*724T>G		3_prime_UTR	Exon 4 of 4	ENSP00000217086.4	Q9UJQ4-1
	ENSG00000303179	ENST00000792520.1		n.231-754A>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.350

AC:

53096

AN:

151544

Hom.:

10652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.555

Gnomad AMI

AF:

0.355

Gnomad AMR

AF:

0.296

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.294

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.293

Gnomad MID

AF:

0.381

Gnomad NFE

AF:

0.259

Gnomad OTH

AF:

0.345

GnomAD4 exome

AF:

0.176

AC:

AN:

306

Hom.:

Cov.:

AF XY:

0.190

AC XY:

AN XY:

174

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.105

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AF:

0.100

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.191

AC:

AN:

236

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.351

AC:

53186

AN:

151666

Hom.:

10677

Cov.:

AF XY:

0.351

AC XY:

25971

AN XY:

74084

show subpopulations

African (AFR)

AF:

0.555

AC:

22942

AN:

41312

American (AMR)

AF:

0.296

AC:

4502

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

1117

AN:

3460

East Asian (EAS)

AF:

0.294

AC:

1515

AN:

5154

South Asian (SAS)

AF:

0.265

AC:

1272

AN:

4806

European-Finnish (FIN)

AF:

0.293

AC:

3081

AN:

10504

Middle Eastern (MID)

AF:

0.386

AC:

112

AN:

290

European-Non Finnish (NFE)

AF:

0.259

AC:

17590

AN:

67920

Other (OTH)

AF:

0.348

AC:

733

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1602

3204

4806

6408

8010

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

490

980

1470

1960

2450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.270

Hom.:

5276

Bravo

AF:

0.359

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.3

(source)

DANN

Benign

0.51

PhyloP100

-0.47

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over