rs199760974

Positions:

• chr16-51141744-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002968.3(SALL1):​c.478G>A​(p.Gly160Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,579,924 control chromosomes in the GnomAD database, including 1 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00088 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (1 hom.)
• Consequence: SALL1 NM_002968.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.86

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=0.004621893).
• BP6: Variant 16-51141744-C-T is Benign according to our data. Variant chr16-51141744-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 258876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-51141744-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00088 (133/151106) while in subpopulation NFE AF= 0.00171 (116/67692). AF 95% confidence interval is 0.00146. There are 0 homozygotes in gnomad4. There are 51 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 133 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL1	NM_002968.3	c.478G>A	p.Gly160Ser	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.478G>A	p.Gly160Ser	missense_variant	2/3	1	NM_002968.3	ENSP00000251020.4

Frequencies

GnomAD3 genomes AF: 0.000881 AC: 133 AN: 150996 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00171

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000871 AC: 186 AN: 213596 Hom.: 0 AF XY: 0.000720 AC XY: 83 AN XY: 115304

Gnomad AFR exome AF: 0.000881

Gnomad AMR exome AF: 0.000170

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000261

Gnomad SAS exome AF: 0.000117

Gnomad FIN exome AF: 0.000108

Gnomad NFE exome AF: 0.00163

Gnomad OTH exome AF: 0.000376

GnomAD4 exome AF: 0.00146 AC: 2081 AN: 1428818 Hom.: 1 Cov.: 49 AF XY: 0.00135 AC XY: 962 AN XY: 710644

Gnomad4 AFR exome AF: 0.000122

Gnomad4 AMR exome AF: 0.0000919

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000208

Gnomad4 SAS exome AF: 0.000143

Gnomad4 FIN exome AF: 0.000193

Gnomad4 NFE exome AF: 0.00181

Gnomad4 OTH exome AF: 0.00131

GnomAD4 genome AF: 0.000880 AC: 133 AN: 151106 Hom.: 0 Cov.: 32 AF XY: 0.000691 AC XY: 51 AN XY: 73818

Gnomad4 AFR AF: 0.000267

Gnomad4 AMR AF: 0.000263

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.000211

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00171

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00106 Hom.: 0

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 07, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2023	SALL1: BP4, BS1 -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Townes syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 03, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.53
DANN	Benign	0.35
DEOGEN2	Benign	0.15	.;T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.29	T;T;T
MetaRNN	Benign	0.0046	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.34	.;N;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.51	N;N;N
REVEL	Benign	0.085
Sift	Benign	0.98	T;T;T
Sift4G	Benign	0.75	T;T;.
Polyphen		0.0010	.;B;.
Vest4		0.12
MVP		0.52
MPC		0.20
ClinPred		0.0086	T
GERP RS		-1.6
Varity_R		0.028
gMVP		0.071

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: rs199760974; hg19: chr16-51175655; COSMIC: COSV51758538; COSMIC: COSV51758538;