1-27949109-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001304579.2(SMPDL3B):c.-299C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,614,102 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: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
SMPDL3B
NM_001304579.2 5_prime_UTR_premature_start_codon_gain
NM_001304579.2 5_prime_UTR_premature_start_codon_gain
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 3.02
Genes affected
SMPDL3B (HGNC:21416): (sphingomyelin phosphodiesterase acid like 3B) Enables phosphoric diester hydrolase activity. Predicted to be involved in membrane lipid catabolic process; negative regulation of inflammatory response; and negative regulation of toll-like receptor signaling pathway. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05149758).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152214Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251434Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135886
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GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727244
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74360
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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 | Oct 25, 2023 | The c.320C>T (p.A107V) alteration is located in exon 3 (coding exon 3) of the SMPDL3B gene. This alteration results from a C to T substitution at nucleotide position 320, causing the alanine (A) at amino acid position 107 to be replaced by a valine (V). 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
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.;L;.
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
P;.;B;P
Vest4
MutPred
Gain of methylation at K102 (P = 0.0698);.;Gain of methylation at K102 (P = 0.0698);Gain of methylation at K102 (P = 0.0698);
MVP
MPC
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at