rs45459896

Positions:

• chr16-51139678-T-C

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.2544A>G​(p.Gln848=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,614,222 control chromosomes in the GnomAD database, including 191 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0090 (12 hom., cov: 32)
  • Exomes 𝑓: 0.014 (179 hom.)
• Consequence: SALL1 NM_002968.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0320

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=-0.72).
• BP6: Variant 16-51139678-T-C is Benign according to our data. Variant chr16-51139678-T-C is described in ClinVar as [Benign]. Clinvar id is 258865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-51139678-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.032 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00901 (1372/152342) while in subpopulation NFE AF= 0.0148 (1008/68036). AF 95% confidence interval is 0.0141. There are 12 homozygotes in gnomad4. There are 644 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1372 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SALL1	NM_002968.3	c.2544A>G	p.Gln848=	synonymous_variant	2/3	ENST00000251020.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SALL1	ENST00000251020.9	c.2544A>G	p.Gln848=	synonymous_variant	2/3	1	NM_002968.3	P2

Frequencies

GnomAD3 genomes AF: 0.00903 AC: 1374 AN: 152224 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00345

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0148

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00913 AC: 2296 AN: 251476 Hom.: 18 AF XY: 0.00918 AC XY: 1247 AN XY: 135908

Gnomad AFR exome AF: 0.00326

Gnomad AMR exome AF: 0.00489

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00242

Gnomad FIN exome AF: 0.00928

Gnomad NFE exome AF: 0.0151

Gnomad OTH exome AF: 0.0106

GnomAD4 exome AF: 0.0140 AC: 20524 AN: 1461880 Hom.: 179 Cov.: 56 AF XY: 0.0138 AC XY: 10020 AN XY: 727242

Gnomad4 AFR exome AF: 0.00266

Gnomad4 AMR exome AF: 0.00548

Gnomad4 ASJ exome AF: 0.00199

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00231

Gnomad4 FIN exome AF: 0.0103

Gnomad4 NFE exome AF: 0.0168

Gnomad4 OTH exome AF: 0.0123

GnomAD4 genome AF: 0.00901 AC: 1372 AN: 152342 Hom.: 12 Cov.: 32 AF XY: 0.00865 AC XY: 644 AN XY: 74488

Gnomad4 AFR AF: 0.00344

Gnomad4 AMR AF: 0.00581

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.00942

Gnomad4 NFE AF: 0.0148

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.0126 Hom.: 7

Bravo AF: 0.00900

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0148

EpiControl AF: 0.0132

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 12, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	SALL1: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Townes syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 16, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.1
DANN	Benign	0.23

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: rs45459896; hg19: chr16-51173589;