rs75156807

Variant names:

• chr16-51141832-C-T
• rs75156807
• NM_002968.3:c.390G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-51141832-C-T
• chr16-51141832-C-A
• chr16-51141832-C-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.390G>A​(p.Pro130Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,613,810 control chromosomes in the GnomAD database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0086 (9 hom., cov: 32)
  • Exomes 𝑓: 0.013 (132 hom.)
• Consequence: SALL1 NM_002968.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.333
• Publications: 5 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=-0.77).
• BP6: Variant 16-51141832-C-T is Benign according to our data. Variant chr16-51141832-C-T is described in ClinVar as Benign. ClinVar VariationId is 258872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.333 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00864 (1315/152152) while in subpopulation NFE AF = 0.0127 (866/67996). AF 95% confidence interval is 0.012. There are 9 homozygotes in GnomAd4. There are 614 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1315 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.390G>A	p.Pro130Pro	synonymous	Exon 2 of 3	NP_002959.2	Q9NSC2-1
	SALL1	NM_001127892.2		c.99G>A	p.Pro33Pro	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.390G>A	p.Pro130Pro	synonymous	Exon 2 of 3	ENSP00000251020.4	Q9NSC2-1
	SALL1	ENST00000566102.1	TSL:1	c.77-4280G>A		intron	N/A	ENSP00000455582.1	H3BQ32
	SALL1	ENST00000440970.6	TSL:5	c.390G>A	p.Pro130Pro	synonymous	Exon 3 of 4	ENSP00000407914.2	Q9NSC2-1

Frequencies

GnomAD3 genomes AF: 0.00865 AC: 1315 AN: 152034 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00287

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00936

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00562

Gnomad FIN AF: 0.00813

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0127

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.00905 AC: 2274 AN: 251316 AF XY: 0.00945

Gnomad AFR exome AF: 0.00297

Gnomad AMR exome AF: 0.00731

Gnomad ASJ exome AF: 0.0120

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00698

Gnomad NFE exome AF: 0.0127

Gnomad OTH exome AF: 0.0106

GnomAD4 exome AF: 0.0125 AC: 18331 AN: 1461658 Hom.: 132 Cov.: 43 AF XY: 0.0123 AC XY: 8919 AN XY: 727124

African (AFR) AF: 0.00218 AC: 73 AN: 33476

American (AMR) AF: 0.00769 AC: 344 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0119 AC: 310 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00605 AC: 522 AN: 86254

European-Finnish (FIN) AF: 0.00779 AC: 416 AN: 53420

Middle Eastern (MID) AF: 0.0115 AC: 64 AN: 5580

European-Non Finnish (NFE) AF: 0.0144 AC: 16001 AN: 1112008

Other (OTH) AF: 0.00992 AC: 599 AN: 60362

GnomAD4 genome AF: 0.00864 AC: 1315 AN: 152152 Hom.: 9 Cov.: 32 AF XY: 0.00826 AC XY: 614 AN XY: 74370

African (AFR) AF: 0.00287 AC: 119 AN: 41516

American (AMR) AF: 0.00935 AC: 143 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00562 AC: 27 AN: 4804

European-Finnish (FIN) AF: 0.00813 AC: 86 AN: 10572

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0127 AC: 866 AN: 67996

Other (OTH) AF: 0.0123 AC: 26 AN: 2114

Alfa AF: 0.0111 Hom.: 6

Bravo AF: 0.00876

Asia WGS AF: 0.00260 AC: 10 AN: 3478

EpiCase AF: 0.0152

EpiControl AF: 0.0156

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	not specified (2)
-	-	1	Townes syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.4
DANN	Benign	0.67
PhyloP100		-0.33
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: rs75156807; hg19: chr16-51175743; COSMIC: COSV51754954; COSMIC: COSV51754954;