4-140396131-T-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4
The NM_004362.3(CLGN):c.959A>G(p.Lys320Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 31)
Consequence
CLGN
NM_004362.3 missense
NM_004362.3 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 2.83
Genes affected
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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;
PP5
Variant 4-140396131-T-C is Pathogenic according to our data. Variant chr4-140396131-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 599571.Status of the report is no_assertion_criteria_provided, 0 stars.
BP4
Computational evidence support a benign effect (MetaRNN=0.11074209). . Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CLGN | NM_004362.3 | c.959A>G | p.Lys320Arg | missense_variant | 9/15 | ENST00000325617.10 | NP_004353.1 | |
CLGN | NM_001130675.2 | c.959A>G | p.Lys320Arg | missense_variant | 10/16 | NP_001124147.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLGN | ENST00000325617.10 | c.959A>G | p.Lys320Arg | missense_variant | 9/15 | 1 | NM_004362.3 | ENSP00000326699 | P1 | |
CLGN | ENST00000414773.5 | c.959A>G | p.Lys320Arg | missense_variant | 10/16 | 1 | ENSP00000392782 | P1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Short stature Pathogenic:1
Likely pathogenic, no assertion criteria provided | case-control | Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg | Nov 18, 2001 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
D;D
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Loss of methylation at K320 (P = 7e-04);Loss of methylation at K320 (P = 7e-04);
MVP
MPC
0.080
ClinPred
T
GERP RS
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