11-557915-C-T

Variant summary

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

The NM_173573.3(LMNTD2):​c.524G>A​(p.Arg175His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000145 in 1,581,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R175C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

LMNTD2
NM_173573.3 missense

Scores

3
1
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.64
Variant links:
Genes affected
LMNTD2 (HGNC:28561): (lamin tail domain containing 2) Predicted to be a structural constituent of chromatin. Predicted to be involved in regulation of chromatin assembly. Predicted to act upstream of or within positive regulation of mRNA splicing, via spliceosome. Predicted to be active in lamin filament. [provided by Alliance of Genome Resources, Apr 2022]
LMNTD2-AS1 (HGNC:41204): (LMNTD2 antisense RNA 1)

Genome browser will be placed here

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=0.35443115).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LMNTD2NM_173573.3 linkc.524G>A p.Arg175His missense_variant Exon 5 of 14 ENST00000329451.8 NP_775844.2 Q8IXW0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LMNTD2ENST00000329451.8 linkc.524G>A p.Arg175His missense_variant Exon 5 of 14 1 NM_173573.3 ENSP00000331167.3 Q8IXW0
LMNTD2ENST00000441853.5 linkc.545G>A p.Arg182His missense_variant Exon 6 of 9 3 ENSP00000393529.1 C9JV74
LMNTD2ENST00000486629.1 linkc.554G>A p.Arg185His missense_variant Exon 5 of 7 5 ENSP00000435529.1 E9PJR3
LMNTD2-AS1ENST00000527620.5 linkn.321C>T non_coding_transcript_exon_variant Exon 1 of 2 2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152212
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000143
AC:
3
AN:
209756
Hom.:
0
AF XY:
0.0000176
AC XY:
2
AN XY:
113722
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000403
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000214
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000154
AC:
22
AN:
1428888
Hom.:
0
Cov.:
35
AF XY:
0.0000184
AC XY:
13
AN XY:
707772
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:
0.0000123
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000182
Gnomad4 OTH exome
AF:
0.0000170
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152212
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000166
AC:
2
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Uncertain
0.048
T
BayesDel_noAF
Benign
-0.17
CADD
Benign
23
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.087
T;T;.
Eigen
Benign
0.088
Eigen_PC
Benign
-0.020
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.75
T;T;T
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.35
T;T;T
MetaSVM
Benign
-1.1
T
PROVEAN
Benign
-2.2
N;D;D
REVEL
Benign
0.28
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;.
Polyphen
1.0
D;.;.
Vest4
0.34
MutPred
0.61
Loss of MoRF binding (P = 0.0258);.;.;
MVP
0.38
MPC
0.43
ClinPred
0.66
D
GERP RS
3.8
RBP_binding_hub_radar
1.0
RBP_regulation_power_radar
2.9
Varity_R
0.19
gMVP
0.097

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: rs765247683; hg19: chr11-557915; COSMIC: COSV54242782; COSMIC: COSV54242782; API