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GeneBe

16-51137123-C-T

Variant summary

Our verdict is Benign. Variant got -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 0.000092 in 152194 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 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: 0.000095 ( 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: 7.89

Links

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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: {Likely_benign=1, Uncertain_significance=2}.
BS1
?
Variant frequency is greater than expected. gnomad 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 gnomad. There are 5 alleles in male gnomad subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 14 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SALL1NM_002968.3 linkuse as main transcriptc.3964G>A p.Val1322Ile missense_variant 3/3 ENST00000251020.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SALL1ENST00000251020.9 linkuse as main transcriptc.3964G>A p.Val1322Ile missense_variant 3/31 NM_002968.3 P2Q9NSC2-1

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152194
Hom.:
0
Cov.:
32
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
GnomAD3 exomes
AF:
0.0000955
AC:
24
AN:
251410
Hom.:
0
AF XY:
0.0000957
AC XY:
13
AN XY:
135898
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 SAS exome
AF:
0.0000653
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.:
0
AF XY:
0.000118
AC XY:
86
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000129
Gnomad4 OTH exome
AF:
0.000182
Alfa
AF:
0.000258
Hom.:
0
Bravo
AF:
0.000128
ExAC
AF:
0.0000494
AC:
6
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 07, 2022The 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
Uncertain significance, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenFeb 01, 2019- -
Townes syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJun 13, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.42
Cadd
Benign
22
Dann
Uncertain
0.99
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.76
T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.19
T;T
MetaSVM
Benign
-0.99
T
MutationTaster
Benign
1.0
D;D;D;D
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
T
GERP RS
5.8
Varity_R
0.099
gMVP
0.22

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: rs199701845; hg19: chr16-51171034; API