16-51135999-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_002968.3(SALL1):c.*1112_*1113insT variant causes a 3 prime UTR change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00424 in 152,008 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (0 hom.)
• Consequence: SALL1 NM_002968.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 8.56

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 16-51135999-C-CA is Benign according to our data. Variant chr16-51135999-C-CA is described in ClinVar as [Likely_benign]. Clinvar id is 319575.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00424 (643/151576) while in subpopulation NFE AF= 0.0068 (461/67832). AF 95% confidence interval is 0.00628. There are 2 homozygotes in gnomad4. There are 332 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 643 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SALL1	NM_002968.3	c.*1112_*1113insT		3_prime_UTR_variant	3/3	ENST00000251020.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SALL1	ENST00000251020.9	c.*1112_*1113insT		3_prime_UTR_variant	3/3	1	NM_002968.3	P2
SALL1	ENST00000685868.1	c.*1112_*1113insT		3_prime_UTR_variant	4/4			P2
SALL1	ENST00000440970.6			downstream_gene_variant		5		P2

Frequencies

GnomAD3 genomes AF: 0.00425 AC: 643 AN: 151458 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.00263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.000626

Gnomad FIN AF: 0.00570

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00680

Gnomad OTH AF: 0.00336

GnomAD4 exome AF: 0.00231 AC: 1 AN: 432 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 260

Gnomad4 FIN exome AF: 0.00235

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00424 AC: 643 AN: 151576 Hom.: 2 Cov.: 33 AF XY: 0.00448 AC XY: 332 AN XY: 74064

Gnomad4 AFR AF: 0.00157

Gnomad4 AMR AF: 0.00262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.000627

Gnomad4 FIN AF: 0.00570

Gnomad4 NFE AF: 0.00680

Gnomad4 OTH AF: 0.00332

Bravo AF: 0.00382

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Townes-Brocks syndrome 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs551203456; hg19: chr16-51169910;