1-226266250-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001366245.2(LIN9):​c.899G>A​(p.Arg300Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000207 in 1,594,044 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 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

LIN9
NM_001366245.2 missense

Scores

2
4
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.63
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16299835).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LIN9NM_001366245.2 linkuse as main transcriptc.899G>A p.Arg300Gln 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.899G>A p.Arg300Gln missense_variant 9/15 NM_001366245.2 ENSP00000505590 Q5TKA1-1

Frequencies

GnomAD3 genomes
AF:
0.0000264
AC:
4
AN:
151710
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000726
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000367
AC:
9
AN:
245282
Hom.:
0
AF XY:
0.0000452
AC XY:
6
AN XY:
132840
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000149
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000134
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000201
AC:
29
AN:
1442220
Hom.:
0
Cov.:
28
AF XY:
0.0000181
AC XY:
13
AN XY:
717604
show subpopulations
Gnomad4 AFR exome
AF:
0.0000606
Gnomad4 AMR exome
AF:
0.000137
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000956
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000100
Gnomad4 OTH exome
AF:
0.0000337
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
151824
Hom.:
0
Cov.:
31
AF XY:
0.0000270
AC XY:
2
AN XY:
74190
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4

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 GeneticsAug 12, 2021The c.947G>A (p.R316Q) alteration is located in exon 9 (coding exon 9) of the LIN9 gene. This alteration results from a G to A substitution at nucleotide position 947, causing the arginine (R) at amino acid position 316 to be replaced by a glutamine (Q). 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
Benign
-0.18
T
BayesDel_noAF
Benign
-0.24
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.025
T;.;T;T
Eigen
Uncertain
0.25
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D;D;D;D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.16
T;T;T;T
MetaSVM
Benign
-0.63
T
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-1.5
N;N;N;N
REVEL
Benign
0.20
Sift
Benign
0.067
T;T;T;T
Sift4G
Benign
0.21
T;T;T;T
Polyphen
1.0
.;.;.;D
Vest4
0.74, 0.74
MVP
0.27
MPC
0.58
ClinPred
0.38
T
GERP RS
4.0
gMVP
0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201671299; hg19: chr1-226453951; API