15-58890403-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_024755.4(SLTM):c.1957G>A(p.Glu653Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000752 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
SLTM
NM_024755.4 missense
NM_024755.4 missense
Scores
6
8
5
Clinical Significance
Conservation
PhyloP100: 7.17
Genes affected
SLTM (HGNC:20709): (SAFB like transcription modulator) Enables RNA binding activity. Predicted to be involved in regulation of mRNA processing and regulation of transcription by RNA polymerase II. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]
RNF111 (HGNC:17384): (ring finger protein 111) The protein encoded by this gene is a nuclear RING-domain containing E3 ubiquitin ligase. This protein interacts with the transforming growth factor (TGF) -beta/NODAL signaling pathway by promoting the ubiquitination and proteosomal degradation of negative regulators, like SMAD proteins, and thereby enhances TGF-beta target-gene transcription. As a modulator of the nodal signaling cascade, this gene plays a critical role in the induction of mesoderm during embryonic development. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLTM | NM_024755.4 | c.1957G>A | p.Glu653Lys | missense_variant | 15/21 | ENST00000380516.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLTM | ENST00000380516.7 | c.1957G>A | p.Glu653Lys | missense_variant | 15/21 | 1 | NM_024755.4 | P1 | |
ENST00000452467.1 | n.277+160C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461798Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727200
GnomAD4 exome
AF:
AC:
11
AN:
1461798
Hom.:
Cov.:
31
AF XY:
AC XY:
5
AN XY:
727200
Gnomad4 AFR exome
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Gnomad4 EAS exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 04, 2022 | The c.1957G>A (p.E653K) alteration is located in exon 15 (coding exon 15) of the SLTM gene. This alteration results from a G to A substitution at nucleotide position 1957, causing the glutamic acid (E) at amino acid position 653 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;T
Polyphen
D;.
Vest4
MutPred
Gain of methylation at E653 (P = 0.0048);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.