NM_002968.3:c.1904C>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.1904C>T(p.Pro635Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00304 in 1,614,090 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P635S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 27 hom. )

Consequence

SALL1
NM_002968.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.57

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: Labcorp Genetics (formerly Invitae), PanelApp Australia, 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=0.0043956935).

BP6

Variant 16-51140318-G-A is Benign according to our data. Variant chr16-51140318-G-A is described in ClinVar as Benign. ClinVar VariationId is 258861.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 = 0.00282 (429/152318) while in subpopulation NFE AF = 0.00375 (255/68030). AF 95% confidence interval is 0.00337. There are 1 homozygotes in GnomAd4. There are 219 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 429 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL1	NM_002968.3	MANE Select	c.1904C>T	p.Pro635Leu	missense	Exon 2 of 3	NP_002959.2	Q9NSC2-1
	SALL1	NM_001127892.2		c.1613C>T	p.Pro538Leu	missense	Exon 2 of 3	NP_001121364.1	Q9NSC2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SALL1	ENST00000251020.9	TSL:1 MANE Select	c.1904C>T	p.Pro635Leu	missense	Exon 2 of 3	ENSP00000251020.4	Q9NSC2-1
SALL1	ENST00000566102.1	TSL:1	c.77-2766C>T		intron	N/A	ENSP00000455582.1	H3BQ32
SALL1	ENST00000440970.6	TSL:5	c.1904C>T	p.Pro635Leu	missense	Exon 3 of 4	ENSP00000407914.2	Q9NSC2-1

Frequencies

GnomAD3 genomes

AF:

0.00282

AC:

429

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0117

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00375

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.00324

AC:

812

AN:

250604

AF XY:

0.00307

show subpopulations

Gnomad AFR exome

AF:

0.000310

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.00152

Gnomad FIN exome

AF:

0.0120

Gnomad NFE exome

AF:

0.00407

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.00306

AC:

4478

AN:

1461772

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

2251

AN XY:

727192

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

33478

American (AMR)

AF:

0.000648

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00142

AC:

AN:

26136

East Asian (EAS)

AF:

0.0116

AC:

460

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0125

AC:

664

AN:

53318

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00283

AC:

3144

AN:

1111996

Other (OTH)

AF:

0.00215

AC:

130

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

294

588

881

1175

1469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

252

336

420

<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:

0.00282

AC:

429

AN:

152318

Hom.:

Cov.:

AF XY:

0.00294

AC XY:

219

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

41578

American (AMR)

AF:

0.000588

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00328

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0117

AC:

124

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00375

AC:

255

AN:

68030

Other (OTH)

AF:

0.000475

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

107

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:

0.00370

Hom.:

Bravo

AF:

0.00190

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00336

AC:

408

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00289

EpiControl

AF:

0.00273

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

SALL1-related disorder (1)

Townes syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.26

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.62

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0044

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.7

PhyloP100

5.6

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.7

REVEL

Benign

0.17

Sift

Benign

0.037

Sift4G

Benign

0.13

Polyphen

0.0

Vest4

0.045

MVP

0.18

MPC

0.22

ClinPred

0.015

GERP RS

1.8

Varity_R

0.031

gMVP

0.22

Mutation Taster

=96/4

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