Genetic Variant SALL1:p.Gly163dup (chr16-51141732-T-TGCC) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_002968.3(SALL1):c.487_489dupGGC(p.Gly163dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00091 in 1,610,550 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00087 ( 1 hom. )

Consequence

SALL1
NM_002968.3 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 2.36

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 -9 ACMG points.

BP6

Variant 16-51141732-T-TGCC is Benign according to our data. Variant chr16-51141732-T-TGCC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 258877.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Benign=2, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00128 (193/150964) while in subpopulation AFR AF= 0.00231 (94/40642). AF 95% confidence interval is 0.00193. There are 0 homozygotes in gnomad4. There are 99 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 193 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL1	NM_002968.3 link	c.487_489dupGGC	p.Gly163dup	conservative_inframe_insertion	Exon 2 of 3	ENST00000251020.9	NP_002959.2	Q9NSC2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SALL1	ENST00000251020.9 link	c.487_489dupGGC	p.Gly163dup	conservative_inframe_insertion	Exon 2 of 3	1	NM_002968.3	ENSP00000251020.4		Q9NSC2-1

Frequencies

GnomAD3 genomes

AF:

0.00128

AC:

193

AN:

150846

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00232

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000657

Gnomad ASJ

AF:

0.00318

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.000421

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000958

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000792

AC:

197

AN:

248582

Hom.:

AF XY:

0.000735

AC XY:

AN XY:

134694

show subpopulations

Gnomad AFR exome

AF:

0.00153

Gnomad AMR exome

AF:

0.000551

Gnomad ASJ exome

AF:

0.00239

Gnomad EAS exome

AF:

0.00109

Gnomad SAS exome

AF:

0.000622

Gnomad FIN exome

AF:

0.0000466

Gnomad NFE exome

AF:

0.000723

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.000872

AC:

1273

AN:

1459586

Hom.:

Cov.:

AF XY:

0.000898

AC XY:

652

AN XY:

726078

show subpopulations

Gnomad4 AFR exome

AF:

0.00189

Gnomad4 AMR exome

AF:

0.000716

Gnomad4 ASJ exome

AF:

0.00310

Gnomad4 EAS exome

AF:

0.00197

Gnomad4 SAS exome

AF:

0.000674

Gnomad4 FIN exome

AF:

0.0000939

Gnomad4 NFE exome

AF:

0.000773

Gnomad4 OTH exome

AF:

0.00144

GnomAD4 genome

AF:

0.00128

AC:

193

AN:

150964

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

AN XY:

73812

show subpopulations

Gnomad4 AFR

AF:

0.00231

Gnomad4 AMR

AF:

0.000656

Gnomad4 ASJ

AF:

0.00318

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.000421

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.000958

Gnomad4 OTH

AF:

0.00143

EpiCase

AF:

0.00158

EpiControl

AF:

0.000654

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 11, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Jun 21, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SALL1: BS1 -

Townes-Brocks syndrome 1

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Townes syndrome

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

16-51141732-TGCCGCC-TGCCGCCGCC

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