chr5-177489402-T-C
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_005451.5(PDLIM7):āc.860A>Gā(p.Lys287Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000436 in 1,583,796 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 (ā ).
Frequency
Genomes: š 0.00013 ( 0 hom., cov: 33)
Exomes š: 0.000034 ( 0 hom. )
Consequence
PDLIM7
NM_005451.5 missense
NM_005451.5 missense
Scores
1
8
8
Clinical Significance
Conservation
PhyloP100: 7.90
Genes affected
PDLIM7 (HGNC:22958): (PDZ and LIM domain 7) The protein encoded by this gene is representative of a family of proteins composed of conserved PDZ and LIM domains. LIM domains are proposed to function in protein-protein recognition in a variety of contexts including gene transcription and development and in cytoskeletal interaction. The LIM domains of this protein bind to protein kinases, whereas the PDZ domain binds to actin filaments. The gene product is involved in the assembly of an actin filament-associated complex essential for transmission of ret/ptc2 mitogenic signaling. The biological function is likely to be that of an adapter, with the PDZ domain localizing the LIM-binding proteins to actin filaments of both skeletal muscle and nonmuscle tissues. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.37518728).
BS2
High AC in GnomAd4 at 20 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDLIM7 | NM_005451.5 | c.860A>G | p.Lys287Arg | missense_variant | 9/13 | ENST00000355841.7 | |
PDLIM7 | NM_203352.3 | c.758A>G | p.Lys253Arg | missense_variant | 9/13 | ||
PDLIM7 | NR_103804.2 | n.1147A>G | non_coding_transcript_exon_variant | 9/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDLIM7 | ENST00000355841.7 | c.860A>G | p.Lys287Arg | missense_variant | 9/13 | 1 | NM_005451.5 | P3 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152172Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000340 AC: 7AN: 205874Hom.: 0 AF XY: 0.0000270 AC XY: 3AN XY: 110918
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GnomAD4 exome AF: 0.0000342 AC: 49AN: 1431506Hom.: 0 Cov.: 30 AF XY: 0.0000310 AC XY: 22AN XY: 709094
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GnomAD4 genome AF: 0.000131 AC: 20AN: 152290Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7AN XY: 74466
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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 | Feb 27, 2024 | The c.860A>G (p.K287R) alteration is located in exon 9 (coding exon 8) of the PDLIM7 gene. This alteration results from a A to G substitution at nucleotide position 860, causing the lysine (K) at amino acid position 287 to be replaced by an arginine (R). 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
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;P
Vest4
MVP
MPC
0.71
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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