Genetic Variant SALL1:c.3535-32_3535-31dupCT (chr16-51137582-C-CAG) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_002968.3(SALL1):c.3535-32_3535-31dupCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000652 in 1,503,168 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

SALL1
NM_002968.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.256

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

Townes-Brocks syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
Townes-Brocks syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SALL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0000864 (13/150440) while in subpopulation AMR AF = 0.000132 (2/15104). AF 95% confidence interval is 0.0000327. There are 0 homozygotes in GnomAd4. There are 8 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL1	NM_002968.3 link	c.3535-32_3535-31dupCT		intron_variant	Intron 2 of 2	ENST00000251020.9	NP_002959.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SALL1	ENST00000251020.9 link	c.3535-31_3535-30insCT		intron_variant	Intron 2 of 2	1	NM_002968.3	ENSP00000251020.4

Frequencies

GnomAD3 genomes

AF:

0.0000798

AC:

AN:

150332

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000733

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000133

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000985

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000740

Gnomad OTH

AF:

0.000487

GnomAD2 exomes

AF:

0.000179

AC:

AN:

156212

AF XY:

0.000164

show subpopulations

Gnomad AFR exome

AF:

0.000112

Gnomad AMR exome

AF:

0.000183

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000146

Gnomad NFE exome

AF:

0.000280

Gnomad OTH exome

AF:

0.000263

GnomAD4 exome

AF:

0.0000628

AC:

AN:

1352728

Hom.:

Cov.:

AF XY:

0.0000650

AC XY:

AN XY:

676818

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000639

AC:

AN:

31298

American (AMR)

AF:

0.0000917

AC:

AN:

43626

Ashkenazi Jewish (ASJ)

AF:

0.0000399

AC:

AN:

25072

East Asian (EAS)

AF:

0.0000780

AC:

AN:

38456

South Asian (SAS)

AF:

0.0000363

AC:

AN:

82668

European-Finnish (FIN)

AF:

0.000143

AC:

AN:

48912

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5530

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

1020664

Other (OTH)

AF:

0.0000885

AC:

AN:

56502

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.354

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000864

AC:

AN:

150440

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

73454

show subpopulations

African (AFR)

AF:

0.0000975

AC:

AN:

41044

American (AMR)

AF:

0.000132

AC:

AN:

15104

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5120

South Asian (SAS)

AF:

0.00

AC:

AN:

4728

European-Finnish (FIN)

AF:

0.0000985

AC:

AN:

10150

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000740

AC:

AN:

67570

Other (OTH)

AF:

0.000482

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.26

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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16-51137582-CAGAG-CAGAGAG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over