16-51141747-T-C

Position:

• chr16-51141747-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002968.3(SALL1):​c.475A>G​(p.Ser159Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0943 in 1,243,758 control chromosomes in the GnomAD database, including 3,526 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S159AA?) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.066 (382 hom., cov: 31)
  • Exomes 𝑓: 0.098 (3144 hom.)
• Consequence: SALL1 NM_002968.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0900

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002341956).
• BP6: Variant 16-51141747-T-C is Benign according to our data. Variant chr16-51141747-T-C is described in ClinVar as [Benign]. Clinvar id is 258875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-51141747-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL1	NM_002968.3	c.475A>G	p.Ser159Gly	missense_variant	2/3	ENST00000251020.9	NP_002959.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SALL1	ENST00000251020.9	c.475A>G	p.Ser159Gly	missense_variant	2/3	1	NM_002968.3	ENSP00000251020.4

Frequencies

GnomAD3 genomes AF: 0.0658 AC: 9726 AN: 147732 Hom.: 382 Cov.: 31

Gnomad AFR AF: 0.0537

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.0377

Gnomad ASJ AF: 0.0377

Gnomad EAS AF: 0.0214

Gnomad SAS AF: 0.0225

Gnomad FIN AF: 0.0879

Gnomad MID AF: 0.0229

Gnomad NFE AF: 0.0841

Gnomad OTH AF: 0.0414

GnomAD3 exomes AF: 0.0679 AC: 12552 AN: 184844 Hom.: 297 AF XY: 0.0685 AC XY: 6867 AN XY: 100214

Gnomad AFR exome AF: 0.0622

Gnomad AMR exome AF: 0.0375

Gnomad ASJ exome AF: 0.0459

Gnomad EAS exome AF: 0.0297

Gnomad SAS exome AF: 0.0345

Gnomad FIN exome AF: 0.0885

Gnomad NFE exome AF: 0.0897

Gnomad OTH exome AF: 0.0763

GnomAD4 exome AF: 0.0981 AC: 107547 AN: 1095922 Hom.: 3144 Cov.: 42 AF XY: 0.0972 AC XY: 52536 AN XY: 540650

Gnomad4 AFR exome AF: 0.0671

Gnomad4 AMR exome AF: 0.0454

Gnomad4 ASJ exome AF: 0.0523

Gnomad4 EAS exome AF: 0.0362

Gnomad4 SAS exome AF: 0.0395

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.0905

GnomAD4 genome AF: 0.0658 AC: 9728 AN: 147836 Hom.: 382 Cov.: 31 AF XY: 0.0646 AC XY: 4670 AN XY: 72256

Gnomad4 AFR AF: 0.0536

Gnomad4 AMR AF: 0.0376

Gnomad4 ASJ AF: 0.0377

Gnomad4 EAS AF: 0.0215

Gnomad4 SAS AF: 0.0226

Gnomad4 FIN AF: 0.0879

Gnomad4 NFE AF: 0.0841

Gnomad4 OTH AF: 0.0410

Alfa AF: 0.0762 Hom.: 147

Bravo AF: 0.0618

ESP6500AA AF: 0.0461 AC: 201

ESP6500EA AF: 0.0630 AC: 540

ExAC AF: 0.0592 AC: 6302

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Townes syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Townes-Brocks syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetics and Molecular Pathology, SA Pathology

May 28, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.73
DANN	Benign	0.21
DEOGEN2	Benign	0.23	.;T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.32	T;T;T
MetaRNN	Benign	0.0023	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.34	.;N;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.43	N;N;N
REVEL	Benign	0.033
Sift	Benign	0.46	T;T;T
Sift4G	Benign	0.45	T;T;.
Polyphen		0.034	.;B;.
Vest4		0.090
MPC		0.18
ClinPred		0.0027	T
GERP RS		-0.37
Varity_R		0.041
gMVP		0.12

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

Publications

LitVar

Other links and lift over

dbSNP: rs13336129; hg19: chr16-51175658; COSMIC: COSV51752690; COSMIC: COSV51752690;