rs374006676

Variant names:

• chr16-51137019-AGGGGC-A
• rs374006676
• NM_002968.3:c.*88_*92delGCCCC

Your query was ambiguous. Multiple possible variants found:

• chr16-51137019-AGGGGC-A
• chr16-51137019-AGGGGC-AGGGGCGGGGC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_002968.3(SALL1):​c.*88_*92delGCCCC 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
• Publications: 0 publications found

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: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Ambry Genetics
• Townes-Brocks syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 319593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 408 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002968.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL1	NM_002968.3	MANE Select	c.*88_*92delGCCCC		3_prime_UTR	Exon 3 of 3	NP_002959.2	Q9NSC2-1
	SALL1	NM_001127892.2		c.*88_*92delGCCCC		3_prime_UTR	Exon 3 of 3	NP_001121364.1	Q9NSC2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL1	ENST00000251020.9	TSL:1 MANE Select	c.*88_*92delGCCCC		3_prime_UTR	Exon 3 of 3	ENSP00000251020.4	Q9NSC2-1
	SALL1	ENST00000440970.6	TSL:5	c.*88_*92delGCCCC		3_prime_UTR	Exon 4 of 4	ENSP00000407914.2	Q9NSC2-1
	SALL1	ENST00000685868.1		c.*88_*92delGCCCC		3_prime_UTR	Exon 4 of 4	ENSP00000509873.1	Q9NSC2-1

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

African (AFR) AF: 0.00994 AC: 224 AN: 22534

American (AMR) AF: 0.000390 AC: 14 AN: 35938

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21630

East Asian (EAS) AF: 0.00 AC: 0 AN: 34308

South Asian (SAS) AF: 0.000103 AC: 7 AN: 68176

European-Finnish (FIN) AF: 0.0000252 AC: 1 AN: 39652

Middle Eastern (MID) AF: 0.000432 AC: 2 AN: 4632

European-Non Finnish (NFE) AF: 0.00000813 AC: 5 AN: 614928

Other (OTH) AF: 0.000730 AC: 30 AN: 41094

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

African (AFR) AF: 0.0313 AC: 388 AN: 12396

American (AMR) AF: 0.00440 AC: 17 AN: 3868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1250

East Asian (EAS) AF: 0.00 AC: 0 AN: 1684

South Asian (SAS) AF: 0.00 AC: 0 AN: 1422

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 84

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 26786

Other (OTH) AF: 0.00441 AC: 3 AN: 680

Alfa AF: 0.0000559 Hom.: 0

Bravo AF: 0.00315

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Townes-Brocks syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs374006676; hg19: chr16-51170930;