dbSNP rs144019351: SALL1:p.Arg726Arg (chr16-51140044-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002968.3(SALL1):c.2178G>A(p.Arg726Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,614,176 control chromosomes in the GnomAD database, including 232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 22 hom., cov: 32)

Exomes 𝑓: 0.014 ( 210 hom. )

Consequence

SALL1
NM_002968.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0880

Publications

4 publications found

Variant links:

Genes affected

SALL1 (HGNC:10524): (spalt like transcription factor 1) The protein encoded by this gene is a zinc finger transcriptional repressor and may be part of the NuRD histone deacetylase complex (HDAC). Defects in this gene are a cause of Townes-Brocks syndrome (TBS) as well as bronchio-oto-renal syndrome (BOR). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SALL1 Gene-Disease associations (from GenCC):

Townes-Brocks syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
Townes-Brocks syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SALL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 16-51140044-C-T is Benign according to our data. Variant chr16-51140044-C-T is described in ClinVar as Benign. ClinVar VariationId is 258862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.088 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0112 (1712/152290) while in subpopulation AMR AF = 0.015 (229/15292). AF 95% confidence interval is 0.0139. There are 22 homozygotes in GnomAd4. There are 789 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1712 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002968.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL1	NM_002968.3	MANE Select	c.2178G>A	p.Arg726Arg	synonymous	Exon 2 of 3	NP_002959.2
	SALL1	NM_001127892.2		c.1887G>A	p.Arg629Arg	synonymous	Exon 2 of 3	NP_001121364.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SALL1	ENST00000251020.9	TSL:1 MANE Select	c.2178G>A	p.Arg726Arg	synonymous	Exon 2 of 3	ENSP00000251020.4
SALL1	ENST00000566102.1	TSL:1	c.77-2492G>A		intron	N/A	ENSP00000455582.1
SALL1	ENST00000440970.6	TSL:5	c.2178G>A	p.Arg726Arg	synonymous	Exon 3 of 4	ENSP00000407914.2

Frequencies

GnomAD3 genomes

AF:

0.0112

AC:

1705

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0149

Gnomad ASJ

AF:

0.0518

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0126

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0146

Gnomad OTH

AF:

0.0172

GnomAD2 exomes

AF:

0.0140

AC:

3511

AN:

251492

AF XY:

0.0134

show subpopulations

Gnomad AFR exome

AF:

0.00258

Gnomad AMR exome

AF:

0.0210

Gnomad ASJ exome

AF:

0.0480

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0131

Gnomad NFE exome

AF:

0.0155

Gnomad OTH exome

AF:

0.0158

GnomAD4 exome

AF:

0.0136

AC:

19809

AN:

1461886

Hom.:

210

Cov.:

AF XY:

0.0133

AC XY:

9690

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00260

AC:

AN:

33480

American (AMR)

AF:

0.0204

AC:

914

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0471

AC:

1232

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00380

AC:

328

AN:

86258

European-Finnish (FIN)

AF:

0.0136

AC:

725

AN:

53420

Middle Eastern (MID)

AF:

0.0309

AC:

178

AN:

5768

European-Non Finnish (NFE)

AF:

0.0139

AC:

15423

AN:

1112004

Other (OTH)

AF:

0.0152

AC:

921

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

1325

2651

3976

5302

6627

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

590

1180

1770

2360

2950

<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:

0.0112

AC:

1712

AN:

152290

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

789

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00277

AC:

115

AN:

41568

American (AMR)

AF:

0.0150

AC:

229

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0518

AC:

180

AN:

3472

East Asian (EAS)

AF:

0.000579

AC:

AN:

5180

South Asian (SAS)

AF:

0.00290

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0126

AC:

134

AN:

10622

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0146

AC:

994

AN:

68010

Other (OTH)

AF:

0.0170

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

182

273

364

455

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0169

Hom.:

Bravo

AF:

0.0125

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jun 09, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jul 10, 2019

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Townes syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

4.8

(source)

DANN

Benign

0.53

PhyloP100

0.088

Mutation Taster

=74/26

polymorphism (auto)

(source)

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over