rs146454164

Positions:

chr16-51140318-G-A

Variant summary

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

The NM_002968.3(SALL1):c.1904C>T(p.Pro635Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00304 in 1,614,090 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 27 hom. )

Consequence

SALL1
NM_002968.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 5.57

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=0.0043956935).

BP6

Variant 16-51140318-G-A is Benign according to our data. Variant chr16-51140318-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 258861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-51140318-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00282 (429/152318) while in subpopulation NFE AF= 0.00375 (255/68030). AF 95% confidence interval is 0.00337. There are 1 homozygotes in gnomad4. There are 219 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 429 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL1	NM_002968.3 linkuse as main transcript	c.1904C>T	p.Pro635Leu	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.1904C>T	p.Pro635Leu	missense_variant	2/3	1	NM_002968.3	ENSP00000251020	P2	Q9NSC2-1

Frequencies

GnomAD3 genomes

AF:

0.00282

AC:

429

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0117

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00375

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.00324

AC:

812

AN:

250604

Hom.:

AF XY:

0.00307

AC XY:

416

AN XY:

135584

show subpopulations

Gnomad AFR exome

AF:

0.000310

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.00152

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0120

Gnomad NFE exome

AF:

0.00407

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.00306

AC:

4478

AN:

1461772

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

2251

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000648

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.0116

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0125

Gnomad4 NFE exome

AF:

0.00283

Gnomad4 OTH exome

AF:

0.00215

GnomAD4 genome

AF:

0.00282

AC:

429

AN:

152318

Hom.:

Cov.:

AF XY:

0.00294

AC XY:

219

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00328

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0117

Gnomad4 NFE

AF:

0.00375

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.00358

Hom.:

Bravo

AF:

0.00190

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00336

AC:

408

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00289

EpiControl

AF:

0.00273

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	SALL1: BP4, BS1 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	- -

SALL1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 03, 2022

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). -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 10, 2020

- -

Townes syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.26

.;T;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.62

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.54

T;T;T

MetaRNN

Benign

0.0044

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.7

.;L;.

MutationTaster

Benign

0.75

D;D;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.17

Sift

Benign

0.037

D;D;D

Sift4G

Benign

0.13

T;T;.

Polyphen

0.0

.;B;.

Vest4

0.045

MVP

0.18

MPC

0.22

ClinPred

0.015

GERP RS

1.8

Varity_R

0.031

gMVP

0.22

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