16-51141744-CGCTGCTGCTGCTGCTGCT-CGCTGCTGCTGCTGCTGCTGCTGCT

Variant summary

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

The NM_002968.3(SALL1):​c.472_477dupAGCAGC​(p.Ser158_Ser159dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,579,948 control chromosomes in the GnomAD database, including 38 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0098 ( 31 hom., cov: 31)
Exomes 𝑓: 0.0012 ( 7 hom. )

Consequence

SALL1
NM_002968.3 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:7

Conservation

PhyloP100: 1.34
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6
Variant 16-51141744-C-CGCTGCT is Benign according to our data. Variant chr16-51141744-C-CGCTGCT is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 319615.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=4}.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00979 (1479/151100) while in subpopulation AFR AF= 0.0334 (1372/41132). AF 95% confidence interval is 0.0319. There are 31 homozygotes in gnomad4. There are 735 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1479 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SALL1NM_002968.3 linkc.472_477dupAGCAGC p.Ser158_Ser159dup conservative_inframe_insertion 2/3 ENST00000251020.9 NP_002959.2 Q9NSC2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SALL1ENST00000251020.9 linkc.472_477dupAGCAGC p.Ser158_Ser159dup conservative_inframe_insertion 2/31 NM_002968.3 ENSP00000251020.4 Q9NSC2-1

Frequencies

GnomAD3 genomes
AF:
0.00978
AC:
1476
AN:
150990
Hom.:
31
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0334
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00408
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000780
Gnomad SAS
AF:
0.00105
Gnomad FIN
AF:
0.000478
Gnomad MID
AF:
0.00641
Gnomad NFE
AF:
0.000236
Gnomad OTH
AF:
0.00625
GnomAD3 exomes
AF:
0.00288
AC:
615
AN:
213596
Hom.:
3
AF XY:
0.00222
AC XY:
256
AN XY:
115304
show subpopulations
Gnomad AFR exome
AF:
0.0309
Gnomad AMR exome
AF:
0.00235
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000653
Gnomad SAS exome
AF:
0.00210
Gnomad FIN exome
AF:
0.000646
Gnomad NFE exome
AF:
0.000423
Gnomad OTH exome
AF:
0.00151
GnomAD4 exome
AF:
0.00124
AC:
1766
AN:
1428848
Hom.:
7
Cov.:
43
AF XY:
0.00106
AC XY:
755
AN XY:
710654
show subpopulations
Gnomad4 AFR exome
AF:
0.0341
Gnomad4 AMR exome
AF:
0.00214
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00278
Gnomad4 SAS exome
AF:
0.00167
Gnomad4 FIN exome
AF:
0.000443
Gnomad4 NFE exome
AF:
0.000128
Gnomad4 OTH exome
AF:
0.00238
GnomAD4 genome
AF:
0.00979
AC:
1479
AN:
151100
Hom.:
31
Cov.:
31
AF XY:
0.00996
AC XY:
735
AN XY:
73818
show subpopulations
Gnomad4 AFR
AF:
0.0334
Gnomad4 AMR
AF:
0.00407
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000782
Gnomad4 SAS
AF:
0.00106
Gnomad4 FIN
AF:
0.000478
Gnomad4 NFE
AF:
0.000236
Gnomad4 OTH
AF:
0.00618

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:7
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not specified Benign:4
Benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Oct 02, 2015- -
Benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxJan 07, 2019- -
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenAug 01, 2024SALL1: BS1, BS2 -
Townes-Brocks syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Townes syndrome Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 04, 2024- -

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.

Other links and lift over

dbSNP: rs113614842; hg19: chr16-51175655; API