16-51141747-T-C

Variant names:

• chr16-51141747-T-C
• rs13336129
• NM_002968.3:c.475A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002968.3(SALL1):​c.475A>G​(p.Ser159Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0943 in 1,243,758 control chromosomes in the GnomAD database, including 3,526 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 Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S159R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.066 (382 hom., cov: 31)
  • Exomes 𝑓: 0.098 (3144 hom.)
• Consequence: SALL1 NM_002968.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0900
• Publications: 17 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002341956).
• BP6: Variant 16-51141747-T-C is Benign according to our data. Variant chr16-51141747-T-C is described in ClinVar as Benign. ClinVar VariationId is 258875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0823 is higher than 0.05.

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.475A>G	p.Ser159Gly	missense	Exon 2 of 3	NP_002959.2
	SALL1	NM_001127892.2		c.184A>G	p.Ser62Gly	missense	Exon 2 of 3	NP_001121364.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL1	ENST00000251020.9	TSL:1 MANE Select	c.475A>G	p.Ser159Gly	missense	Exon 2 of 3	ENSP00000251020.4
	SALL1	ENST00000566102.1	TSL:1	c.77-4195A>G		intron	N/A	ENSP00000455582.1
	SALL1	ENST00000440970.6	TSL:5	c.475A>G	p.Ser159Gly	missense	Exon 3 of 4	ENSP00000407914.2

Frequencies

GnomAD3 genomes AF: 0.0658 AC: 9726 AN: 147732 Hom.: 382 Cov.: 31

Gnomad AFR AF: 0.0537

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.0377

Gnomad ASJ AF: 0.0377

Gnomad EAS AF: 0.0214

Gnomad SAS AF: 0.0225

Gnomad FIN AF: 0.0879

Gnomad MID AF: 0.0229

Gnomad NFE AF: 0.0841

Gnomad OTH AF: 0.0414

GnomAD2 exomes AF: 0.0679 AC: 12552 AN: 184844 AF XY: 0.0685

Gnomad AFR exome AF: 0.0622

Gnomad AMR exome AF: 0.0375

Gnomad ASJ exome AF: 0.0459

Gnomad EAS exome AF: 0.0297

Gnomad FIN exome AF: 0.0885

Gnomad NFE exome AF: 0.0897

Gnomad OTH exome AF: 0.0763

GnomAD4 exome AF: 0.0981 AC: 107547 AN: 1095922 Hom.: 3144 Cov.: 42 AF XY: 0.0972 AC XY: 52536 AN XY: 540650

African (AFR) AF: 0.0671 AC: 1679 AN: 25030

American (AMR) AF: 0.0454 AC: 1328 AN: 29244

Ashkenazi Jewish (ASJ) AF: 0.0523 AC: 917 AN: 17530

East Asian (EAS) AF: 0.0362 AC: 924 AN: 25494

South Asian (SAS) AF: 0.0395 AC: 2259 AN: 57216

European-Finnish (FIN) AF: 0.116 AC: 4420 AN: 37986

Middle Eastern (MID) AF: 0.0383 AC: 158 AN: 4122

European-Non Finnish (NFE) AF: 0.107 AC: 91913 AN: 855662

Other (OTH) AF: 0.0905 AC: 3949 AN: 43638

GnomAD4 genome AF: 0.0658 AC: 9728 AN: 147836 Hom.: 382 Cov.: 31 AF XY: 0.0646 AC XY: 4670 AN XY: 72256

African (AFR) AF: 0.0536 AC: 2186 AN: 40754

American (AMR) AF: 0.0376 AC: 559 AN: 14854

Ashkenazi Jewish (ASJ) AF: 0.0377 AC: 127 AN: 3372

East Asian (EAS) AF: 0.0215 AC: 110 AN: 5128

South Asian (SAS) AF: 0.0226 AC: 107 AN: 4742

European-Finnish (FIN) AF: 0.0879 AC: 897 AN: 10204

Middle Eastern (MID) AF: 0.0211 AC: 6 AN: 284

European-Non Finnish (NFE) AF: 0.0841 AC: 5513 AN: 65548

Other (OTH) AF: 0.0410 AC: 84 AN: 2048

Alfa AF: 0.0762 Hom.: 147

Bravo AF: 0.0618

ESP6500AA AF: 0.0461 AC: 201

ESP6500EA AF: 0.0630 AC: 540

ExAC AF: 0.0592 AC: 6302

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Mar 03, 2015

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Townes-Brocks syndrome 1 Benign:1

May 28, 2020

Genetics and Molecular Pathology, SA Pathology

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.73
DANN	Benign	0.21
DEOGEN2	Benign	0.23	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.090
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.033
Sift	Benign	0.46	T
Sift4G	Benign	0.45	T
Polyphen		0.034	B
Vest4		0.090
MPC		0.18
ClinPred		0.0027	T
GERP RS		-0.37
Varity_R		0.041
gMVP		0.12
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13336129; hg19: chr16-51175658; COSMIC: COSV51752690; COSMIC: COSV51752690;