chr16-51141413-G-A

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.809C>T(p.Pro270Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000533 in 1,614,132 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00092 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00049 ( 6 hom. )

Consequence

SALL1
NM_002968.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.41

Publications

3 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=0.005468607).

BP6

Variant 16-51141413-G-A is Benign according to our data. Variant chr16-51141413-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 282089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000919 (140/152334) while in subpopulation EAS AF = 0.0224 (116/5178). AF 95% confidence interval is 0.0191. There are 1 homozygotes in GnomAd4. There are 75 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 140 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL1	NM_002968.3 link	c.809C>T	p.Pro270Leu	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.809C>T	p.Pro270Leu	missense_variant	Exon 2 of 3	1	NM_002968.3	ENSP00000251020.4		Q9NSC2-1

Frequencies

GnomAD3 genomes

AF:

0.000920

AC:

140

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0224

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00163

AC:

410

AN:

251432

AF XY:

0.00143

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0209

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000493

AC:

721

AN:

1461798

Hom.:

Cov.:

AF XY:

0.000477

AC XY:

347

AN XY:

727192

show subpopulations

African (AFR)

AF:

0.000239

AC:

AN:

33476

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0147

AC:

582

AN:

39700

South Asian (SAS)

AF:

0.000487

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.00000719

AC:

AN:

1112010

Other (OTH)

AF:

0.00132

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

115

173

230

288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000919

AC:

140

AN:

152334

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41576

American (AMR)

AF:

0.000261

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0224

AC:

116

AN:

5178

South Asian (SAS)

AF:

0.00145

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.000244

Hom.:

Bravo

AF:

0.000873

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00141

AC:

171

Asia WGS

AF:

0.0130

AC:

AN:

3478

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

May 04, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Aug 19, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Townes syndrome

Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.57

.;D;T

Eigen

Benign

-0.037

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.90

D;D;D

MetaRNN

Benign

0.0055

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.7

.;L;.

PhyloP100

6.4

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-2.2

N;N;N

REVEL

Benign

0.078

Sift

Uncertain

0.0040

D;D;D

Sift4G

Benign

0.32

T;T;.

Polyphen

0.047

.;B;.

Vest4

0.29

MVP

0.15

MPC

0.24

ClinPred

0.029

GERP RS

4.8

Varity_R

0.17

gMVP

0.43

Mutation Taster

=95/5

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