16-20920126-C-A

Variant summary

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

The NM_001128302.3(LYRM1):​c.164C>A​(p.Thr55Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,608,126 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LYRM1
NM_001128302.3 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.19
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.164C>A p.Thr55Lys missense_variant Exon 3 of 4 ENST00000567954.6 NP_001121774.1 O43325A0A024R3C2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LYRM1ENST00000567954.6 linkc.164C>A p.Thr55Lys missense_variant Exon 3 of 4 1 NM_001128302.3 ENSP00000457333.1 O43325

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152116
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1456010
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
724628
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152116
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74280
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 09, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.164C>A (p.T55K) alteration is located in exon 4 (coding exon 2) of the LYRM1 gene. This alteration results from a C to A substitution at nucleotide position 164, causing the threonine (T) at amino acid position 55 to be replaced by a lysine (K). 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
0.097
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.050
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.14
T;T;T;T;T;T
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.78
.;.;.;T;.;.
M_CAP
Benign
0.057
D
MetaRNN
Uncertain
0.65
D;D;D;D;D;D
MetaSVM
Uncertain
-0.20
T
MutationAssessor
Benign
1.9
M;M;M;M;M;M
PrimateAI
Uncertain
0.60
T
PROVEAN
Uncertain
-3.5
D;D;D;D;D;D
REVEL
Uncertain
0.53
Sift
Benign
0.044
D;D;D;D;D;D
Sift4G
Benign
0.16
T;T;T;T;T;T
Polyphen
0.96
P;P;P;P;P;P
Vest4
0.61
MutPred
0.52
Gain of MoRF binding (P = 0.0362);Gain of MoRF binding (P = 0.0362);Gain of MoRF binding (P = 0.0362);Gain of MoRF binding (P = 0.0362);Gain of MoRF binding (P = 0.0362);Gain of MoRF binding (P = 0.0362);
MVP
0.81
MPC
0.28
ClinPred
0.98
D
GERP RS
5.8
Varity_R
0.51
gMVP
0.73

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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: rs759338347; hg19: chr16-20931448; API