rs139646526

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002968.3(SALL1):c.472A>G(p.Ser158Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,517,888 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 6 hom. )

Consequence

SALL1
NM_002968.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.491

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003352046).

BP6

Variant 16-51141750-T-C is Benign according to our data. Variant chr16-51141750-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 258873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00384 (581/151210) while in subpopulation AFR AF= 0.00883 (365/41322). AF 95% confidence interval is 0.00809. There are 5 homozygotes in gnomad4. There are 270 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 581 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL1	NM_002968.3 linkuse as main transcript	c.472A>G	p.Ser158Gly	missense_variant	2/3	ENST00000251020.9	NP_002959.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SALL1	ENST00000251020.9 linkuse as main transcript	c.472A>G	p.Ser158Gly	missense_variant	2/3	1	NM_002968.3	ENSP00000251020	P2	Q9NSC2-1

Frequencies

GnomAD3 genomes

AF:

0.00385

AC:

582

AN:

151094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00888

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.00125

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000948

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00165

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00135

AC:

330

AN:

243684

Hom.:

AF XY:

0.00138

AC XY:

183

AN XY:

132414

show subpopulations

Gnomad AFR exome

AF:

0.00730

Gnomad AMR exome

AF:

0.000651

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00118

Gnomad SAS exome

AF:

0.000600

Gnomad FIN exome

AF:

0.0000469

Gnomad NFE exome

AF:

0.00134

Gnomad OTH exome

AF:

0.00170

GnomAD4 exome

AF:

0.00200

AC:

2733

AN:

1366678

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

1360

AN XY:

679754

show subpopulations

Gnomad4 AFR exome

AF:

0.00874

Gnomad4 AMR exome

AF:

0.000747

Gnomad4 ASJ exome

AF:

0.0000401

Gnomad4 EAS exome

AF:

0.000875

Gnomad4 SAS exome

AF:

0.000756

Gnomad4 FIN exome

AF:

0.000230

Gnomad4 NFE exome

AF:

0.00210

Gnomad4 OTH exome

AF:

0.00229

GnomAD4 genome

AF:

0.00384

AC:

581

AN:

151210

Hom.:

Cov.:

AF XY:

0.00365

AC XY:

270

AN XY:

73920

show subpopulations

Gnomad4 AFR

AF:

0.00883

Gnomad4 AMR

AF:

0.00125

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000966

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000948

Gnomad4 NFE

AF:

0.00165

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00164

Hom.:

Bravo

AF:

0.00477

ESP6500AA

AF:

0.00344

AC:

ESP6500EA

AF:

0.000702

AC:

ExAC

AF:

0.00166

AC:

198

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 22, 2015	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. -

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	SALL1: BP4, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

SALL1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 23, 2021

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Townes syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 28, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.57

DANN

Benign

0.089

DEOGEN2

Benign

0.17

.;T;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.34

T;T;T

MetaRNN

Benign

0.0034

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

.;N;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.13

N;N;N

REVEL

Benign

0.040

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.45

T;T;.

Polyphen

0.0080

.;B;.

Vest4

0.10

MVP

0.35

MPC

0.18

ClinPred

0.0016

GERP RS

-0.45

Varity_R

0.039

gMVP

0.13

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