4-25802299-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015187.5(SEL1L3):c.1940C>T(p.Thr647Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,010 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
SEL1L3
NM_015187.5 missense
NM_015187.5 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 3.48
Genes affected
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.21972203).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEL1L3 | NM_015187.5 | c.1940C>T | p.Thr647Ile | missense_variant | 11/24 | ENST00000399878.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEL1L3 | ENST00000399878.8 | c.1940C>T | p.Thr647Ile | missense_variant | 11/24 | 1 | NM_015187.5 | P1 | |
SEL1L3 | ENST00000264868.9 | c.1835C>T | p.Thr612Ile | missense_variant | 11/24 | 1 | |||
SEL1L3 | ENST00000502949.5 | c.1481C>T | p.Thr494Ile | missense_variant | 11/24 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248456Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134814
GnomAD3 exomes
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248456
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461010Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 726790
GnomAD4 exome
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31
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726790
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ExAC
?
AF:
AC:
1
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 | Aug 31, 2022 | The c.1940C>T (p.T647I) alteration is located in exon 11 (coding exon 11) of the SEL1L3 gene. This alteration results from a C to T substitution at nucleotide position 1940, causing the threonine (T) at amino acid position 647 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Uncertain
D;D;D
Polyphen
D;.;.
Vest4
MutPred
Loss of disorder (P = 0.0255);.;.;
MVP
MPC
ClinPred
T
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