16-20924012-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001128302.3(LYRM1):​c.265C>T​(p.Pro89Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000484 in 1,446,532 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

LYRM1
NM_001128302.3 missense

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.09
Variant links:
Genes affected
LYRM1 (HGNC:25074): (LYR motif containing 1) The protein encoded by this gene belongs to the mitochondrial leucine/tyrosine/arginine motif family of proteins. Proteins of this family are short polypeptides that contain a leucine/tyrosine/arginine motif near the N-terminus. This gene is widely expressed with high levels in omental adipose tissue of obese individuals. In adipose tissue, the protein is localized to the nucleus where it promotes preadipocyte proliferation and lowers the rate of apoptosis to regulate adipose tissue homeostasis. Overexpression of this gene in adipocytes causes abnormal mitochondrial morphology and mitochondrial dysfunction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

Genome browser will be placed here

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;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LYRM1NM_001128302.3 linkc.265C>T p.Pro89Ser missense_variant Exon 4 of 4 ENST00000567954.6 NP_001121774.1 O43325A0A024R3C2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LYRM1ENST00000567954.6 linkc.265C>T p.Pro89Ser missense_variant Exon 4 of 4 1 NM_001128302.3 ENSP00000457333.1 O43325

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000484
AC:
7
AN:
1446532
Hom.:
0
Cov.:
27
AF XY:
0.00000278
AC XY:
2
AN XY:
720274
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:
0.00000635
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.265C>T (p.P89S) alteration is located in exon 5 (coding exon 3) of the LYRM1 gene. This alteration results from a C to T substitution at nucleotide position 265, causing the proline (P) at amino acid position 89 to be replaced by a serine (S). 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
AlphaMissense
Benign
0.30
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.10
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.12
T;T;T;T;T;T
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.93
.;.;.;D;.;.
M_CAP
Benign
0.010
T
MetaRNN
Uncertain
0.48
T;T;T;T;T;T
MetaSVM
Benign
-0.32
T
MutationAssessor
Uncertain
2.2
M;M;M;M;M;M
PrimateAI
Uncertain
0.59
T
PROVEAN
Uncertain
-3.4
D;D;D;D;D;D
REVEL
Uncertain
0.57
Sift
Benign
0.14
T;T;T;T;T;T
Sift4G
Uncertain
0.052
T;T;T;T;T;T
Polyphen
0.98
D;D;D;D;D;D
Vest4
0.64
MutPred
0.30
Loss of catalytic residue at P88 (P = 0.0099);Loss of catalytic residue at P88 (P = 0.0099);Loss of catalytic residue at P88 (P = 0.0099);Loss of catalytic residue at P88 (P = 0.0099);Loss of catalytic residue at P88 (P = 0.0099);Loss of catalytic residue at P88 (P = 0.0099);
MVP
0.18
MPC
0.33
ClinPred
0.96
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.24
gMVP
0.70

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: rs2083340604; hg19: chr16-20935334; API