5-154456003-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_024632.6(SAP30L):c.527C>T(p.Ser176Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,613,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
SAP30L
NM_024632.6 missense
NM_024632.6 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 4.07
Genes affected
SAP30L (HGNC:25663): (SAP30 like) Enables several functions, including non-sequence-specific DNA binding activity, bending; phosphatidylinositol phosphate binding activity; and zinc ion binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in fibrillar center and nucleoplasm. Part of histone deacetylase complex. [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=0.024960816).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SAP30L | NM_024632.6 | c.527C>T | p.Ser176Leu | missense_variant | 4/4 | ENST00000297109.11 | NP_078908.1 | |
SAP30L | NM_001131062.2 | c.404C>T | p.Ser135Leu | missense_variant | 3/3 | NP_001124534.1 | ||
SAP30L | NM_001131063.2 | c.389C>T | p.Ser130Leu | missense_variant | 3/3 | NP_001124535.1 | ||
SAP30L | NR_024084.2 | n.1179C>T | non_coding_transcript_exon_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SAP30L | ENST00000297109.11 | c.527C>T | p.Ser176Leu | missense_variant | 4/4 | 1 | NM_024632.6 | ENSP00000297109.5 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152124Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000319 AC: 8AN: 251106Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135730
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461620Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727120
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74436
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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 | Jun 29, 2023 | The c.527C>T (p.S176L) alteration is located in exon 4 (coding exon 4) of the SAP30L gene. This alteration results from a C to T substitution at nucleotide position 527, causing the serine (S) at amino acid position 176 to be replaced by a leucine (L). 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
Benign
DANN
Benign
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
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