16-51137123-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2

The NM_002968.3(SALL1):c.3964G>A(p.Val1322Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000111 in 1,614,060 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). Synonymous variant affecting the same amino acid position (i.e. V1322V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

SALL1
NM_002968.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.89

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 was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19055453).

BP6

Variant 16-51137123-C-T is Benign according to our data. Variant chr16-51137123-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 808043.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000092 (14/152194) while in subpopulation NFE AF = 0.000162 (11/68044). AF 95% confidence interval is 0.0000905. There are 0 homozygotes in GnomAd4. There are 5 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL1	NM_002968.3 link	c.3964G>A	p.Val1322Ile	missense_variant	Exon 3 of 3	ENST00000251020.9	NP_002959.2	Q9NSC2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SALL1	ENST00000251020.9 link	c.3964G>A	p.Val1322Ile	missense_variant	Exon 3 of 3	1	NM_002968.3	ENSP00000251020.4		Q9NSC2-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000955

AC:

AN:

251410

AF XY:

0.0000957

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000113

AC:

165

AN:

1461866

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

33480

Gnomad4 AMR exome

AF:

0.0000224

AC:

AN:

44724

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26136

Gnomad4 EAS exome

AF:

0.0000504

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.0000696

AC:

AN:

86258

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53410

Gnomad4 NFE exome

AF:

0.000129

AC:

143

AN:

1111996

Gnomad4 Remaining exome

AF:

0.000182

AC:

AN:

60394

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0000724

AC:

0.0000723694

AN:

0.0000723694

Gnomad4 AMR

AF:

0.00

AC:

AN:

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000162

AC:

0.00016166

AN:

0.00016166

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000251

Hom.:

Bravo

AF:

0.000128

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.3964G>A (p.V1322I) alteration is located in exon 3 (coding exon 3) of the SALL1 gene. This alteration results from a G to A substitution at nucleotide position 3964, causing the valine (V) at amino acid position 1322 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Feb 01, 2019

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Townes syndrome

Benign:1

Jun 13, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.48

.;T

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

.;L

PROVEAN

Benign

-0.69

N;N

REVEL

Benign

0.12

Sift

Uncertain

0.011

D;D

Sift4G

Uncertain

0.018

D;D

Polyphen

0.66

.;P

Vest4

0.24

MVP

0.23

MPC

0.17

ClinPred

0.14

GERP RS

5.8

Varity_R

0.099

gMVP

0.22

Mutation Taster

=57/43

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

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