16-51141744-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002968.3(SALL1):c.478G>A(p.Gly160Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,579,924 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00088 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 1 hom. )

Consequence

SALL1
NM_002968.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.86

Publications

5 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004621893).

BP6

Variant 16-51141744-C-T is Benign according to our data. Variant chr16-51141744-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00088 (133/151106) while in subpopulation NFE AF = 0.00171 (116/67692). AF 95% confidence interval is 0.00146. There are 0 homozygotes in GnomAd4. There are 51 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 133 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL1	NM_002968.3 link	c.478G>A	p.Gly160Ser	missense_variant	Exon 2 of 3	ENST00000251020.9	NP_002959.2	Q9NSC2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SALL1	ENST00000251020.9 link	c.478G>A	p.Gly160Ser	missense_variant	Exon 2 of 3	1	NM_002968.3	ENSP00000251020.4		Q9NSC2-1

Frequencies

GnomAD3 genomes

AF:

0.000881

AC:

133

AN:

150996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000268

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.000211

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00171

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000871

AC:

186

AN:

213596

AF XY:

0.000720

show subpopulations

Gnomad AFR exome

AF:

0.000881

Gnomad AMR exome

AF:

0.000170

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.000108

Gnomad NFE exome

AF:

0.00163

Gnomad OTH exome

AF:

0.000376

GnomAD4 exome

AF:

0.00146

AC:

2081

AN:

1428818

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

962

AN XY:

710644

show subpopulations

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

African (AFR)

AF:

0.000122

AC:

AN:

32714

American (AMR)

AF:

0.0000919

AC:

AN:

43538

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25464

East Asian (EAS)

AF:

0.000208

AC:

AN:

38528

South Asian (SAS)

AF:

0.000143

AC:

AN:

83984

European-Finnish (FIN)

AF:

0.000193

AC:

AN:

51878

Middle Eastern (MID)

AF:

0.000183

AC:

AN:

5450

European-Non Finnish (NFE)

AF:

0.00181

AC:

1965

AN:

1088450

Other (OTH)

AF:

0.00131

AC:

AN:

58812

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

108

216

325

433

541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<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:

0.000880

AC:

133

AN:

151106

Hom.:

Cov.:

AF XY:

0.000691

AC XY:

AN XY:

73818

show subpopulations

African (AFR)

AF:

0.000267

AC:

AN:

41142

American (AMR)

AF:

0.000263

AC:

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.000195

AC:

AN:

5116

South Asian (SAS)

AF:

0.000211

AC:

AN:

4736

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10452

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00171

AC:

116

AN:

67692

Other (OTH)

AF:

0.00

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000986

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SALL1: BP4, BS1 -

Apr 07, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Townes syndrome

Benign:1

Oct 29, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.53

(source)

DANN

Benign

0.35

DEOGEN2

Benign

0.15

.;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.29

T;T;T

MetaRNN

Benign

0.0046

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.34

.;N;.

PhyloP100

1.9

PrimateAI

Benign

0.32

PROVEAN

Benign

0.51

N;N;N

REVEL

Benign

0.085

Sift

Benign

0.98

T;T;T

Sift4G

Benign

0.75

T;T;.

Polyphen

0.0010

.;B;.

Vest4

0.12

MVP

0.52

MPC

0.20

ClinPred

0.0086

GERP RS

-1.6

Varity_R

0.028

gMVP

0.071

Mutation Taster

=100/0

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over