rs144019351

Variant names:

• chr16-51140044-C-T
• rs144019351
• NM_002968.3:c.2178G>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002968.3(SALL1):​c.2178G>A​(p.Arg726Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,614,176 control chromosomes in the GnomAD database, including 232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (22 hom., cov: 32)
  • Exomes 𝑓: 0.014 (210 hom.)
• Consequence: SALL1 NM_002968.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0880

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=-0.55).
• BP6: Variant 16-51140044-C-T is Benign according to our data. Variant chr16-51140044-C-T is described in ClinVar as [Benign]. Clinvar id is 258862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-51140044-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.088 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0112 (1712/152290) while in subpopulation AMR AF= 0.015 (229/15292). AF 95% confidence interval is 0.0139. There are 22 homozygotes in gnomad4. There are 789 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1712 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL1	NM_002968.3	c.2178G>A	p.Arg726Arg	synonymous_variant	Exon 2 of 3	ENST00000251020.9	NP_002959.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SALL1	ENST00000251020.9	c.2178G>A	p.Arg726Arg	synonymous_variant	Exon 2 of 3	1	NM_002968.3	ENSP00000251020.4

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1705 AN: 152172 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.00273

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.0518

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0146

Gnomad OTH AF: 0.0172

GnomAD3 exomes AF: 0.0140 AC: 3511 AN: 251492 Hom.: 45 AF XY: 0.0134 AC XY: 1816 AN XY: 135920

Gnomad AFR exome AF: 0.00258

Gnomad AMR exome AF: 0.0210

Gnomad ASJ exome AF: 0.0480

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00369

Gnomad FIN exome AF: 0.0131

Gnomad NFE exome AF: 0.0155

Gnomad OTH exome AF: 0.0158

GnomAD4 exome AF: 0.0136 AC: 19809 AN: 1461886 Hom.: 210 Cov.: 53 AF XY: 0.0133 AC XY: 9690 AN XY: 727246

Gnomad4 AFR exome AF: 0.00260

Gnomad4 AMR exome AF: 0.0204

Gnomad4 ASJ exome AF: 0.0471

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00380

Gnomad4 FIN exome AF: 0.0136

Gnomad4 NFE exome AF: 0.0139

Gnomad4 OTH exome AF: 0.0152

GnomAD4 genome AF: 0.0112 AC: 1712 AN: 152290 Hom.: 22 Cov.: 32 AF XY: 0.0106 AC XY: 789 AN XY: 74474

Gnomad4 AFR AF: 0.00277

Gnomad4 AMR AF: 0.0150

Gnomad4 ASJ AF: 0.0518

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.0126

Gnomad4 NFE AF: 0.0146

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0169 Hom.: 11

Bravo AF: 0.0125

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Jun 09, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Jul 10, 2019

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Townes syndrome Benign:1

Feb 03, 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
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.8
DANN	Benign	0.53

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: rs144019351; hg19: chr16-51173955;