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16-51137149-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_002968.3(SALL1):c.3938G>A(p.Arg1313His) variant causes a missense change. The variant allele was found at a frequency of 0.0000657 in 152152 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting interpretations of pathogenicity (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1313C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

SALL1
NM_002968.3 missense

Scores

1
5
10

Clinical Significance

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

Conservation

PhyloP100: 5.02

Links

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
Computational evidence support a benign effect (MetaRNN=0.05746132).
BP6
?
Variant 16-51137149-C-T is Benign according to our data. Variant chr16-51137149-C-T is described in ClinVar as [Conflicting_interpretations_of_pathogenicity]. Clinvar id is 426902. Status of the report is criteria_provided_conflicting_interpretations, 1 stars. We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1}.
BS1
?
Variant frequency is greater than expected. gnomad allele frequency = 0.0000657 (10/152152) while in subpopulation EAS AF= 0.000772 (4/5182). AF 95% confidence interval is 0.000263. There are 0 homozygotes in gnomad. There are 3 alleles in male gnomad subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAd at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SALL1NM_002968.3 linkuse as main transcriptc.3938G>A p.Arg1313His missense_variant 3/3 ENST00000251020.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SALL1ENST00000251020.9 linkuse as main transcriptc.3938G>A p.Arg1313His missense_variant 3/31 NM_002968.3 P2Q9NSC2-1

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152152
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000772
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000676
AC:
17
AN:
251458
Hom.:
0
AF XY:
0.0000589
AC XY:
8
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000707
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1461886
Hom.:
0
AF XY:
0.0000124
AC XY:
9
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000227
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.0000166
Alfa
AF:
0.0000386
Hom.:
0
Bravo
AF:
0.0000831
ExAC
AF:
0.0000494
AC:
6
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Townes syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeJan 01, 2023In 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 426902). This variant has not been reported in the literature in individuals affected with SALL1-related conditions. This variant is present in population databases (rs529030284, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1313 of the SALL1 protein (p.Arg1313His). -
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 12, 2022The c.3938G>A (p.R1313H) 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 3938, causing the arginine (R) at amino acid position 1313 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 15, 2021This variant is associated with the following publications: (PMID: 26257827) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.084
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Uncertain
-0.080
Cadd
Uncertain
24
Dann
Uncertain
0.99
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.057
T;T
MetaSVM
Benign
-0.78
T
MutationTaster
Benign
1.0
D;D;D;D
PROVEAN
Benign
-1.5
N;N
REVEL
Benign
0.29
Sift
Benign
0.45
T;T
Sift4G
Benign
0.59
T;T
Polyphen
1.0
.;D
Vest4
0.28
MVP
0.56
MPC
0.26
ClinPred
0.11
T
GERP RS
5.8
Varity_R
0.17
gMVP
0.47

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: rs529030284; hg19: chr16-51171060; COSMIC: COSV51762292; COSMIC: COSV51762292; API