Variant rs864621971 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP5BP4BS1_SupportingBS2

The NM_002968.3(SALL1):c.949C>T(p.Pro317Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

SALL1
NM_002968.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:2

Conservation

PhyloP100: 5.72

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP5

Variant 16-51141273-G-A is Pathogenic according to our data. Variant chr16-51141273-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 208167.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=2, Pathogenic=1}.

BP4

Computational evidence support a benign effect (MetaRNN=0.26929903). . Strength limited to SUPPORTING due to the PP5.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00000616 (9/1461820) while in subpopulation AMR AF= 0.0000894 (4/44724). AF 95% confidence interval is 0.0000298. There are 0 homozygotes in gnomad4_exome. There are 3 alleles in male gnomad4_exome subpopulation. Median coverage is 53. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SALL1	NM_002968.3 linkuse as main transcript	c.949C>T	p.Pro317Ser	missense_variant	2/3	ENST00000251020.9	NP_002959.2	Q9NSC2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SALL1	ENST00000251020.9 linkuse as main transcript	c.949C>T	p.Pro317Ser	missense_variant	2/3	1	NM_002968.3	ENSP00000251020.4		Q9NSC2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251486

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461820

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Townes-Brocks syndrome 1

Pathogenic:1Uncertain:1

Uncertain significance, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Pathogenic, criteria provided, single submitter	research	Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília	Apr 01, 2015	- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Apr 14, 2022

In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31589614, 26380986) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

.;T;T

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.0096

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

.;M;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.014

D;D;D

Sift4G

Benign

0.14

T;T;.

Polyphen

0.78

.;P;.

Vest4

0.41

MutPred

0.26

.;Loss of catalytic residue at P317 (P = 7e-04);.;

MVP

0.26

MPC

0.61

ClinPred

0.65

GERP RS

4.5

Varity_R

0.17

gMVP

0.37

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over