rs138635817

Positions:

chr16-51141843-C-G

Variant summary

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

The NM_002968.3(SALL1):c.379G>C(p.Val127Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00298 in 1,613,892 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 9 hom. )

Consequence

SALL1
NM_002968.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.74

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=0.0036643744).

BP6

Variant 16-51141843-C-G is Benign according to our data. Variant chr16-51141843-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 258870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00198 (301/152238) while in subpopulation AMR AF= 0.00248 (38/15294). AF 95% confidence interval is 0.00199. There are 0 homozygotes in gnomad4. There are 130 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 301 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL1	NM_002968.3 link	c.379G>C	p.Val127Leu	missense_variant	2/3	ENST00000251020.9	NP_002959.2	Q9NSC2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SALL1	ENST00000251020.9 link	c.379G>C	p.Val127Leu	missense_variant	2/3	1	NM_002968.3	ENSP00000251020.4		Q9NSC2-1

Frequencies

GnomAD3 genomes

AF:

0.00199

AC:

302

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00229

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00227

AC:

571

AN:

251398

Hom.:

AF XY:

0.00219

AC XY:

298

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.000617

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.0189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00264

Gnomad OTH exome

AF:

0.00408

GnomAD4 exome

AF:

0.00309

AC:

4512

AN:

1461654

Hom.:

Cov.:

AF XY:

0.00303

AC XY:

2204

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.0194

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.00332

Gnomad4 OTH exome

AF:

0.00345

GnomAD4 genome

AF:

0.00198

AC:

301

AN:

152238

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

130

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000795

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.0193

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00228

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00382

Hom.:

Bravo

AF:

0.00228

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00395

AC:

ExAC

AF:

0.00196

AC:

238

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2024	SALL1: BP4, BS1 -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 31, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 19, 2016	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 12, 2019	This variant is associated with the following publications: (PMID: 24429398) -

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

Labcorp Genetics (formerly Invitae), Labcorp

Dec 30, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.24

.;T;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.0037

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;L;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.58

N;N;N

REVEL

Benign

0.046

Sift

Benign

0.14

T;T;T

Sift4G

Benign

0.50

T;T;.

Polyphen

0.0

.;B;.

Vest4

0.061

MutPred

0.19

.;Loss of sheet (P = 0.0457);.;

MVP

0.25

MPC

0.20

ClinPred

0.0054

GERP RS

0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.072

gMVP

0.098

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