chr16-51137019-AGGGGC-A

Position:

• chr16-51137019-AGGGGC-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_002968.3(SALL1):​c.*88_*92del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000741 in 933,008 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0081 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00032 (3 hom.)
• Consequence: SALL1 NM_002968.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.65

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 -16 ACMG points.

• BP6: Variant 16-51137019-AGGGGC-A is Benign according to our data. Variant chr16-51137019-AGGGGC-A is described in ClinVar as [Likely_benign]. Clinvar id is 319593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-51137019-AGGGGC-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00814 (408/50116) while in subpopulation AFR AF= 0.0313 (388/12396). AF 95% confidence interval is 0.0287. There are 1 homozygotes in gnomad4. There are 200 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 408 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL1	NM_002968.3	c.*88_*92del		3_prime_UTR_variant	3/3	ENST00000251020.9	NP_002959.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SALL1	ENST00000251020.9	c.*88_*92del		3_prime_UTR_variant	3/3	1	NM_002968.3	ENSP00000251020	P2
SALL1	ENST00000440970.6	c.*88_*92del		3_prime_UTR_variant	4/4	5		ENSP00000407914	P2
SALL1	ENST00000685868.1	c.*88_*92del		3_prime_UTR_variant	4/4			ENSP00000509873	P2
SALL1	ENST00000566102.1			downstream_gene_variant		1		ENSP00000455582

Frequencies

GnomAD3 genomes AF: 0.00813 AC: 407 AN: 50078 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.0313

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00440

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00446

GnomAD4 exome AF: 0.000321 AC: 283 AN: 882892 Hom.: 3 AF XY: 0.000302 AC XY: 137 AN XY: 454038

Gnomad4 AFR exome AF: 0.00994

Gnomad4 AMR exome AF: 0.000390

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000103

Gnomad4 FIN exome AF: 0.0000252

Gnomad4 NFE exome AF: 0.00000813

Gnomad4 OTH exome AF: 0.000730

GnomAD4 genome AF: 0.00814 AC: 408 AN: 50116 Hom.: 1 Cov.: 0 AF XY: 0.00857 AC XY: 200 AN XY: 23330

Gnomad4 AFR AF: 0.0313

Gnomad4 AMR AF: 0.00440

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00441

Alfa AF: 0.0000559 Hom.: 0

Bravo AF: 0.00315

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 31, 2019

- -

Townes-Brocks syndrome 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs374006676; hg19: chr16-51170930;