rs138635817

chr16-51141843-C-G

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.379G>C(p.Val127Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00298 in 1,613,892 control chromosomes in the GnomAD database, including 9 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 0.0020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (9 hom.)
• Consequence: SALL1 NM_002968.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.74

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=0.0036643744).
• BP6: Variant 16-51141843-C-G is Benign according to our data. Variant chr16-51141843-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 258870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00198 (301/152238) while in subpopulation AMR AF= 0.00248 (38/15294). AF 95% confidence interval is 0.00199. There are 0 homozygotes in gnomad4. There are 130 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 302 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SALL1	NM_002968.3	c.379G>C	p.Val127Leu	missense_variant	2/3	ENST00000251020.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SALL1	ENST00000251020.9	c.379G>C	p.Val127Leu	missense_variant	2/3	1	NM_002968.3	P2

Frequencies

GnomAD3 genomes AF: 0.00199 AC: 302 AN: 152120 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000797

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00229

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00227 AC: 571 AN: 251398 Hom.: 2 AF XY: 0.00219 AC XY: 298 AN XY: 135902

Gnomad AFR exome AF: 0.000617

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.0189

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000359

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00264

Gnomad OTH exome AF: 0.00408

GnomAD4 exome AF: 0.00309 AC: 4512 AN: 1461654 Hom.: 9 Cov.: 42 AF XY: 0.00303 AC XY: 2204 AN XY: 727116

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.00114

Gnomad4 ASJ exome AF: 0.0194

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000267

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.00332

Gnomad4 OTH exome AF: 0.00345

GnomAD4 genome AF: 0.00198 AC: 301 AN: 152238 Hom.: 0 Cov.: 32 AF XY: 0.00175 AC XY: 130 AN XY: 74440

Gnomad4 AFR AF: 0.000795

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00228

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00382 Hom.: 2

Bravo AF: 0.00228

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.000455 AC: 2

ESP6500EA AF: 0.00395 AC: 34

ExAC AF: 0.00196 AC: 238

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 12, 2019	This variant is associated with the following publications: (PMID: 24429398) -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	SALL1: BP4, BS1 -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 31, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 19, 2016	- -

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

Invitae

Dec 30, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	17
Dann	Benign	0.96
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.0037	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.80	D;D;D;D
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.58	N;N;N
REVEL	Benign	0.046
Sift	Benign	0.14	T;T;T
Sift4G	Benign	0.50	T;T;.
Polyphen		0.0	.;B;.
Vest4		0.061
MutPred		0.19		.;Loss of sheet (P = 0.0457);.;
MVP		0.25
MPC		0.20
ClinPred		0.0054	T
GERP RS		0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.072
gMVP		0.098

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: rs138635817; hg19: chr16-51175754;