chr16-51137215-T-C

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.3872A>G(p.Asn1291Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,614,114 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 14 hom., cov: 31)

Exomes 𝑓: 0.013 ( 150 hom. )

Consequence

SALL1
NM_002968.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.426

Publications

8 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=0.0030624866).

BP6

Variant 16-51137215-T-C is Benign according to our data. Variant chr16-51137215-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 218510.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 = 0.0102 (1552/152236) while in subpopulation NFE AF = 0.0164 (1117/68008). AF 95% confidence interval is 0.0156. There are 14 homozygotes in GnomAd4. There are 714 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 1552 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.3872A>G	p.Asn1291Ser	missense	Exon 3 of 3	NP_002959.2
	SALL1	NM_001127892.2		c.3581A>G	p.Asn1194Ser	missense	Exon 3 of 3	NP_001121364.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SALL1	ENST00000251020.9	TSL:1 MANE Select	c.3872A>G	p.Asn1291Ser	missense	Exon 3 of 3	ENSP00000251020.4
SALL1	ENST00000566102.1	TSL:1	c.*309A>G		3_prime_UTR	Exon 2 of 2	ENSP00000455582.1
SALL1	ENST00000440970.6	TSL:5	c.3872A>G	p.Asn1291Ser	missense	Exon 4 of 4	ENSP00000407914.2

Frequencies

GnomAD3 genomes

AF:

0.0102

AC:

1554

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00338

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00903

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00707

Gnomad FIN

AF:

0.00772

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0164

Gnomad OTH

AF:

0.00960

GnomAD2 exomes

AF:

0.0103

AC:

2583

AN:

251466

AF XY:

0.0108

show subpopulations

Gnomad AFR exome

AF:

0.00295

Gnomad AMR exome

AF:

0.00882

Gnomad ASJ exome

AF:

0.00397

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00892

Gnomad NFE exome

AF:

0.0148

Gnomad OTH exome

AF:

0.0125

GnomAD4 exome

AF:

0.0130

AC:

19051

AN:

1461878

Hom.:

150

Cov.:

AF XY:

0.0130

AC XY:

9478

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00296

AC:

AN:

33480

American (AMR)

AF:

0.00926

AC:

414

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

113

AN:

26136

East Asian (EAS)

AF:

0.000101

AC:

AN:

39700

South Asian (SAS)

AF:

0.00765

AC:

660

AN:

86258

European-Finnish (FIN)

AF:

0.00848

AC:

453

AN:

53420

Middle Eastern (MID)

AF:

0.0158

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0149

AC:

16578

AN:

1111996

Other (OTH)

AF:

0.0106

AC:

639

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1166

2331

3497

4662

5828

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

584

1168

1752

2336

2920

<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:

0.0102

AC:

1552

AN:

152236

Hom.:

Cov.:

AF XY:

0.00959

AC XY:

714

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00337

AC:

140

AN:

41554

American (AMR)

AF:

0.00902

AC:

138

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3468

East Asian (EAS)

AF:

0.000387

AC:

AN:

5172

South Asian (SAS)

AF:

0.00666

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00772

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0164

AC:

1117

AN:

68008

Other (OTH)

AF:

0.00950

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

156

235

313

391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0118

Hom.:

Bravo

AF:

0.00968

TwinsUK

AF:

0.0146

AC:

ALSPAC

AF:

0.0150

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.0155

AC:

133

ExAC

AF:

0.0100

AC:

1220

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0154

EpiControl

AF:

0.0159

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

not specified (2)

Townes-Brocks syndrome 1 (2)

Townes syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.0020

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.14

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.48

PhyloP100

0.43

PROVEAN

Benign

0.66

REVEL

Benign

0.19

Sift

Benign

1.0

Sift4G

Benign

0.70

Polyphen

0.0

Vest4

0.070

MPC

0.16

ClinPred

0.0018

GERP RS

-2.4

Varity_R

0.024

gMVP

0.19

Mutation Taster

=98/2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over