chr16-51137215-T-C

Position:

chr16-51137215-T-C

Variant summary

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

The NM_002968.3(SALL1):c.3872A>G(p.Asn1291Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,614,114 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 14 hom., cov: 31)

Exomes 𝑓: 0.013 ( 150 hom. )

Consequence

SALL1
NM_002968.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.426

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=0.0030624866).

BP6

Variant 16-51137215-T-C is Benign according to our data. Variant chr16-51137215-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 218510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-51137215-T-C is described in Lovd as [Benign]. Variant chr16-51137215-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0102 (1552/152236) while in subpopulation NFE AF= 0.0164 (1117/68008). AF 95% confidence interval is 0.0156. There are 14 homozygotes in gnomad4. There are 714 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1552 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL1	NM_002968.3 linkuse as main transcript	c.3872A>G	p.Asn1291Ser	missense_variant	3/3	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.3872A>G	p.Asn1291Ser	missense_variant	3/3	1	NM_002968.3	ENSP00000251020	P2	Q9NSC2-1

Frequencies

GnomAD3 genomes

AF:

0.0102

AC:

1554

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00338

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00903

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00707

Gnomad FIN

AF:

0.00772

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0164

Gnomad OTH

AF:

0.00960

GnomAD3 exomes

AF:

0.0103

AC:

2583

AN:

251466

Hom.:

AF XY:

0.0108

AC XY:

1474

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00295

Gnomad AMR exome

AF:

0.00882

Gnomad ASJ exome

AF:

0.00397

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00774

Gnomad FIN exome

AF:

0.00892

Gnomad NFE exome

AF:

0.0148

Gnomad OTH exome

AF:

0.0125

GnomAD4 exome

AF:

0.0130

AC:

19051

AN:

1461878

Hom.:

150

Cov.:

AF XY:

0.0130

AC XY:

9478

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00296

Gnomad4 AMR exome

AF:

0.00926

Gnomad4 ASJ exome

AF:

0.00432

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00765

Gnomad4 FIN exome

AF:

0.00848

Gnomad4 NFE exome

AF:

0.0149

Gnomad4 OTH exome

AF:

0.0106

GnomAD4 genome

AF:

0.0102

AC:

1552

AN:

152236

Hom.:

Cov.:

AF XY:

0.00959

AC XY:

714

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00337

Gnomad4 AMR

AF:

0.00902

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00666

Gnomad4 FIN

AF:

0.00772

Gnomad4 NFE

AF:

0.0164

Gnomad4 OTH

AF:

0.00950

Alfa

AF:

0.0129

Hom.:

Bravo

AF:

0.00968

TwinsUK

AF:

0.0146

AC:

ALSPAC

AF:

0.0150

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.0155

AC:

133

ExAC

AF:

0.0100

AC:

1220

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0154

EpiControl

AF:

0.0159

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 02, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	SALL1: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Dec 31, 2014	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Townes-Brocks syndrome 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -

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

0.053

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.0020

DANN

Benign

0.42

DEOGEN2

Benign

0.14

.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.54

T;T

MetaRNN

Benign

0.0031

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.48

.;N

MutationTaster

Benign

0.98

D;N;N;N

PROVEAN

Benign

0.66

N;N

REVEL

Benign

0.19

Sift

Benign

1.0

T;T

Sift4G

Benign

0.70

T;T

Polyphen

0.0

.;B

Vest4

0.070

MPC

0.16

ClinPred

0.0018

GERP RS

-2.4

Varity_R

0.024

gMVP

0.19

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