rs45459896

Variant names:

• chr16-51139678-T-C
• rs45459896
• NM_002968.3:c.2544A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002968.3(SALL1):​c.2544A>G​(p.Gln848Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,614,222 control chromosomes in the GnomAD database, including 191 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0090 (12 hom., cov: 32)
  • Exomes 𝑓: 0.014 (179 hom.)
• Consequence: SALL1 NM_002968.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0320
• Publications: 4 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 16-51139678-T-C is Benign according to our data. Variant chr16-51139678-T-C is described in ClinVar as Benign. ClinVar VariationId is 258865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.032 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00901 (1372/152342) while in subpopulation NFE AF = 0.0148 (1008/68036). AF 95% confidence interval is 0.0141. There are 12 homozygotes in GnomAd4. There are 644 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1372 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.2544A>G	p.Gln848Gln	synonymous	Exon 2 of 3	NP_002959.2	Q9NSC2-1
	SALL1	NM_001127892.2		c.2253A>G	p.Gln751Gln	synonymous	Exon 2 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.2544A>G	p.Gln848Gln	synonymous	Exon 2 of 3	ENSP00000251020.4	Q9NSC2-1
	SALL1	ENST00000566102.1	TSL:1	c.77-2126A>G		intron	N/A	ENSP00000455582.1	H3BQ32
	SALL1	ENST00000440970.6	TSL:5	c.2544A>G	p.Gln848Gln	synonymous	Exon 3 of 4	ENSP00000407914.2	Q9NSC2-1

Frequencies

GnomAD3 genomes AF: 0.00903 AC: 1374 AN: 152224 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00345

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0148

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00913 AC: 2296 AN: 251476 AF XY: 0.00918

Gnomad AFR exome AF: 0.00326

Gnomad AMR exome AF: 0.00489

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00928

Gnomad NFE exome AF: 0.0151

Gnomad OTH exome AF: 0.0106

GnomAD4 exome AF: 0.0140 AC: 20524 AN: 1461880 Hom.: 179 Cov.: 56 AF XY: 0.0138 AC XY: 10020 AN XY: 727242

African (AFR) AF: 0.00266 AC: 89 AN: 33480

American (AMR) AF: 0.00548 AC: 245 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00199 AC: 52 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00231 AC: 199 AN: 86258

European-Finnish (FIN) AF: 0.0103 AC: 552 AN: 53420

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5768

European-Non Finnish (NFE) AF: 0.0168 AC: 18632 AN: 1111998

Other (OTH) AF: 0.0123 AC: 740 AN: 60396

GnomAD4 genome AF: 0.00901 AC: 1372 AN: 152342 Hom.: 12 Cov.: 32 AF XY: 0.00865 AC XY: 644 AN XY: 74488

African (AFR) AF: 0.00344 AC: 143 AN: 41582

American (AMR) AF: 0.00581 AC: 89 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4820

European-Finnish (FIN) AF: 0.00942 AC: 100 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0148 AC: 1008 AN: 68036

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.0126 Hom.: 7

Bravo AF: 0.00900

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0148

EpiControl AF: 0.0132

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	not specified (1)
-	-	1	Townes syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.1
DANN	Benign	0.23
PhyloP100		0.032
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs45459896; hg19: chr16-51173589;