1-226266235-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001366245.2(LIN9):ā€‹c.914C>Gā€‹(p.Pro305Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,433,676 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: not found (cov: 31)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

LIN9
NM_001366245.2 missense

Scores

1
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.09
Variant links:
Genes affected
LIN9 (HGNC:30830): (lin-9 DREAM MuvB core complex component) This gene encodes a tumor suppressor protein that inhibits DNA synthesis and oncogenic transformation through association with the retinoblastoma 1 protein. The encoded protein also interacts with a complex of other cell cycle regulators to repress cell cycle-dependent gene expression in non-dividing cells. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36088705).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LIN9NM_001366245.2 linkuse as main transcriptc.914C>G p.Pro305Arg missense_variant 9/15 ENST00000681046.1 NP_001353174.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LIN9ENST00000681046.1 linkuse as main transcriptc.914C>G p.Pro305Arg missense_variant 9/15 NM_001366245.2 ENSP00000505590 Q5TKA1-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000140
AC:
2
AN:
1433676
Hom.:
0
Cov.:
28
AF XY:
0.00000140
AC XY:
1
AN XY:
713310
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000183
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

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 submitterclinical testingAmbry GeneticsDec 14, 2023The c.962C>G (p.P321R) alteration is located in exon 9 (coding exon 9) of the LIN9 gene. This alteration results from a C to G substitution at nucleotide position 962, causing the proline (P) at amino acid position 321 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
0.050
T
BayesDel_noAF
Benign
-0.17
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.026
T;.;T;T
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.030
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.86
D;D;D;D
M_CAP
Benign
0.0074
T
MetaRNN
Benign
0.36
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-1.6
N;N;N;N
REVEL
Benign
0.17
Sift
Benign
0.032
D;T;D;T
Sift4G
Benign
0.29
T;T;T;T
Polyphen
0.45
.;.;.;P
Vest4
0.57, 0.52
MVP
0.18
MPC
1.1
ClinPred
0.96
D
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-226453936; API