rs144019351

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002968.3(SALL1):c.2178G>A(p.Arg726=) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0880

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 GnomAd at 1705 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SALL1	NM_002968.3 linkuse as main transcript	c.2178G>A	p.Arg726=	synonymous_variant	2/3	ENST00000251020.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SALL1	ENST00000251020.9 linkuse as main transcript	c.2178G>A	p.Arg726=	synonymous_variant	2/3	1	NM_002968.3	P2	Q9NSC2-1

Frequencies

GnomAD3 genomes

AF:

0.0112

AC:

1705

AN:

152172

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0134

AC XY:

1816

AN XY:

135920

show subpopulations

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.:

AF XY:

0.0133

AC XY:

9690

AN XY:

727246

show subpopulations

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.:

Cov.:

AF XY:

0.0106

AC XY:

789

AN XY:

74474

show subpopulations

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.:

Bravo

AF:

0.0125

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2017	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. -

Townes syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Jul 10, 2019

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over