16-51137019-AGGGGC-AGGGGCGGGGC

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002968.3(SALL1):​c.*88_*92dupGCCCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0263 in 932,742 control chromosomes in the GnomAD database, including 462 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.063 (48 hom., cov: 31)
  • Exomes 𝑓: 0.024 (414 hom.)
• Consequence: SALL1 NM_002968.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.456
• 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 -10 ACMG points.

• BP6: Variant 16-51137019-A-AGGGGC is Benign according to our data. Variant chr16-51137019-A-AGGGGC is described in ClinVar as Benign. ClinVar VariationId is 1249227.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

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_*92dupGCCCC		3_prime_UTR	Exon 3 of 3	NP_002959.2	Q9NSC2-1
	SALL1	NM_001127892.2		c.*88_*92dupGCCCC		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_*92dupGCCCC		3_prime_UTR	Exon 3 of 3	ENSP00000251020.4	Q9NSC2-1
	SALL1	ENST00000440970.6	TSL:5	c.*88_*92dupGCCCC		3_prime_UTR	Exon 4 of 4	ENSP00000407914.2	Q9NSC2-1
	SALL1	ENST00000685868.1		c.*88_*92dupGCCCC		3_prime_UTR	Exon 4 of 4	ENSP00000509873.1	Q9NSC2-1

Frequencies

GnomAD3 genomes AF: 0.0628 AC: 3141 AN: 50002 Hom.: 48 Cov.: 31

Gnomad AFR AF: 0.0181

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.0892

Gnomad ASJ AF: 0.0544

Gnomad EAS AF: 0.00119

Gnomad SAS AF: 0.0105

Gnomad FIN AF: 0.0494

Gnomad MID AF: 0.0568

Gnomad NFE AF: 0.0864

Gnomad OTH AF: 0.0685

GnomAD4 exome AF: 0.0242 AC: 21374 AN: 882702 Hom.: 414 Cov.: 12 AF XY: 0.0237 AC XY: 10745 AN XY: 453942

African (AFR) AF: 0.00603 AC: 136 AN: 22536

American (AMR) AF: 0.0201 AC: 724 AN: 35936

Ashkenazi Jewish (ASJ) AF: 0.0214 AC: 462 AN: 21628

East Asian (EAS) AF: 0.0000583 AC: 2 AN: 34308

South Asian (SAS) AF: 0.00392 AC: 267 AN: 68176

European-Finnish (FIN) AF: 0.0142 AC: 562 AN: 39644

Middle Eastern (MID) AF: 0.00345 AC: 16 AN: 4632

European-Non Finnish (NFE) AF: 0.0298 AC: 18309 AN: 614754

Other (OTH) AF: 0.0218 AC: 896 AN: 41088

GnomAD4 genome AF: 0.0627 AC: 3138 AN: 50040 Hom.: 48 Cov.: 31 AF XY: 0.0601 AC XY: 1399 AN XY: 23292

African (AFR) AF: 0.0181 AC: 224 AN: 12388

American (AMR) AF: 0.0890 AC: 344 AN: 3866

Ashkenazi Jewish (ASJ) AF: 0.0544 AC: 68 AN: 1250

East Asian (EAS) AF: 0.00119 AC: 2 AN: 1684

South Asian (SAS) AF: 0.0105 AC: 15 AN: 1424

European-Finnish (FIN) AF: 0.0494 AC: 79 AN: 1600

Middle Eastern (MID) AF: 0.0476 AC: 4 AN: 84

European-Non Finnish (NFE) AF: 0.0863 AC: 2307 AN: 26720

Other (OTH) AF: 0.0676 AC: 46 AN: 680

Alfa AF: 0.00453 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.46
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; COSMIC: COSV51755238; COSMIC: COSV51755238;