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GeneBe

16-51137150-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_002968.3(SALL1):c.3937C>T(p.Arg1313Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000046 in 152116 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1313H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

SALL1
NM_002968.3 missense

Scores

3
9
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.84

Links

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BS1
?
Variant frequency is greater than expected. gnomad allele frequency = 0.000046 (7/152116) while in subpopulation AMR AF= 0.0000655 (1/15268). AF 95% confidence interval is 0. There are 0 homozygotes in gnomad. There are 4 alleles in male gnomad subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
?
High AC in GnomAd at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SALL1NM_002968.3 linkuse as main transcriptc.3937C>T p.Arg1313Cys missense_variant 3/3 ENST00000251020.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SALL1ENST00000251020.9 linkuse as main transcriptc.3937C>T p.Arg1313Cys missense_variant 3/31 NM_002968.3 P2Q9NSC2-1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152116
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251458
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
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:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000219
AC:
32
AN:
1461892
Hom.:
0
AF XY:
0.0000206
AC XY:
15
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000270
Gnomad4 OTH exome
AF:
0.00
Alfa
AF:
0.0000987
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Townes syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeJun 04, 2022In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1313 of the SALL1 protein (p.Arg1313Cys). This variant is present in population databases (rs199883962, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with SALL1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Pathogenic
0.15
Cadd
Pathogenic
30
Dann
Uncertain
0.99
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.023
T
MetaRNN
Uncertain
0.56
D;D
MetaSVM
Benign
-0.58
T
MutationTaster
Benign
1.0
D;D;D;D
PROVEAN
Pathogenic
-4.8
D;D
REVEL
Uncertain
0.34
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0060
D;D
Polyphen
1.0
.;D
Vest4
0.59
MutPred
0.53
.;Loss of disorder (P = 0.0162);
MVP
0.56
MPC
0.32
ClinPred
0.85
D
GERP RS
4.8
Varity_R
0.49
gMVP
0.50

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.

Other links and lift over

dbSNP: rs199883962; hg19: chr16-51171061; API