rs11645288

chr16-51138766-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002968.3(SALL1):c.3456C>T(p.His1152=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,613,986 control chromosomes in the GnomAD database, including 31,502 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3100 hom., cov: 33)
  • Exomes 𝑓: 0.19 (28402 hom.)
• Consequence: SALL1 NM_002968.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0450

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 16-51138766-G-A is Benign according to our data. Variant chr16-51138766-G-A is described in ClinVar as [Benign]. Clinvar id is 258868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-51138766-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.045 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SALL1	NM_002968.3	c.3456C>T	p.His1152=	synonymous_variant	2/3	ENST00000251020.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SALL1	ENST00000251020.9	c.3456C>T	p.His1152=	synonymous_variant	2/3	1	NM_002968.3	P2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29778 AN: 152070 Hom.: 3096 Cov.: 33

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.0337

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.215

GnomAD3 exomes AF: 0.183 AC: 46040 AN: 251406 Hom.: 4721 AF XY: 0.185 AC XY: 25154 AN XY: 135864

Gnomad AFR exome AF: 0.180

Gnomad AMR exome AF: 0.132

Gnomad ASJ exome AF: 0.268

Gnomad EAS exome AF: 0.0328

Gnomad SAS exome AF: 0.143

Gnomad FIN exome AF: 0.258

Gnomad NFE exome AF: 0.211

Gnomad OTH exome AF: 0.207

GnomAD4 exome AF: 0.192 AC: 280177 AN: 1461798 Hom.: 28402 Cov.: 35 AF XY: 0.191 AC XY: 139235 AN XY: 727188

Gnomad4 AFR exome AF: 0.185

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.270

Gnomad4 EAS exome AF: 0.0253

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.251

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.196 AC: 29796 AN: 152188 Hom.: 3100 Cov.: 33 AF XY: 0.196 AC XY: 14610 AN XY: 74406

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.0334

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.213

Alfa AF: 0.205 Hom.: 6719

Bravo AF: 0.187

Asia WGS AF: 0.0830 AC: 288 AN: 3478

EpiCase AF: 0.217

EpiControl AF: 0.216

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Townes syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Townes-Brocks syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	4.1
Dann	Benign	0.56

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

LitVar

Other links and lift over

dbSNP: rs11645288; hg19: chr16-51172677;