chr11-557617-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_173573.3(LMNTD2):​c.579G>A​(p.Met193Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 1,613,194 control chromosomes in the GnomAD database, including 1,311 homozygotes. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.037 ( 108 hom., cov: 33)
Exomes 𝑓: 0.038 ( 1203 hom. )

Consequence

LMNTD2
NM_173573.3 missense

Scores

1
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.459
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 Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0018461645).
BA1
GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0839 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LMNTD2NM_173573.3 linkc.579G>A p.Met193Ile missense_variant Exon 6 of 14 ENST00000329451.8 NP_775844.2 Q8IXW0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LMNTD2ENST00000329451.8 linkc.579G>A p.Met193Ile missense_variant Exon 6 of 14 1 NM_173573.3 ENSP00000331167.3 Q8IXW0
LMNTD2ENST00000441853.5 linkc.600G>A p.Met200Ile missense_variant Exon 7 of 9 3 ENSP00000393529.1 C9JV74
LMNTD2ENST00000486629.1 linkc.609G>A p.Met203Ile missense_variant Exon 6 of 7 5 ENSP00000435529.1 E9PJR3
LMNTD2-AS1ENST00000527620.5 linkn.23C>T non_coding_transcript_exon_variant Exon 1 of 2 2

Frequencies

GnomAD3 genomes
AF:
0.0369
AC:
5617
AN:
152170
Hom.:
108
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0302
Gnomad AMI
AF:
0.0439
Gnomad AMR
AF:
0.0329
Gnomad ASJ
AF:
0.0521
Gnomad EAS
AF:
0.00597
Gnomad SAS
AF:
0.0300
Gnomad FIN
AF:
0.0624
Gnomad MID
AF:
0.0728
Gnomad NFE
AF:
0.0397
Gnomad OTH
AF:
0.0388
GnomAD3 exomes
AF:
0.0371
AC:
9293
AN:
250348
Hom.:
223
AF XY:
0.0381
AC XY:
5170
AN XY:
135618
show subpopulations
Gnomad AFR exome
AF:
0.0289
Gnomad AMR exome
AF:
0.0247
Gnomad ASJ exome
AF:
0.0509
Gnomad EAS exome
AF:
0.00604
Gnomad SAS exome
AF:
0.0369
Gnomad FIN exome
AF:
0.0622
Gnomad NFE exome
AF:
0.0407
Gnomad OTH exome
AF:
0.0467
GnomAD4 exome
AF:
0.0383
AC:
56003
AN:
1460906
Hom.:
1203
Cov.:
36
AF XY:
0.0386
AC XY:
28047
AN XY:
726728
show subpopulations
Gnomad4 AFR exome
AF:
0.0300
Gnomad4 AMR exome
AF:
0.0264
Gnomad4 ASJ exome
AF:
0.0534
Gnomad4 EAS exome
AF:
0.00539
Gnomad4 SAS exome
AF:
0.0367
Gnomad4 FIN exome
AF:
0.0643
Gnomad4 NFE exome
AF:
0.0383
Gnomad4 OTH exome
AF:
0.0420
GnomAD4 genome
AF:
0.0369
AC:
5625
AN:
152288
Hom.:
108
Cov.:
33
AF XY:
0.0379
AC XY:
2825
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.0302
Gnomad4 AMR
AF:
0.0329
Gnomad4 ASJ
AF:
0.0521
Gnomad4 EAS
AF:
0.00598
Gnomad4 SAS
AF:
0.0298
Gnomad4 FIN
AF:
0.0624
Gnomad4 NFE
AF:
0.0397
Gnomad4 OTH
AF:
0.0393
Alfa
AF:
0.0307
Hom.:
34
Bravo
AF:
0.0353
TwinsUK
AF:
0.0399
AC:
148
ALSPAC
AF:
0.0355
AC:
137
ESP6500AA
AF:
0.0284
AC:
125
ESP6500EA
AF:
0.0408
AC:
351
ExAC
AF:
0.0374
AC:
4535
EpiCase
AF:
0.0463
EpiControl
AF:
0.0446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Benign
-0.58
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
15
DANN
Benign
0.97
DEOGEN2
Benign
0.043
T;T;.
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.038
N
LIST_S2
Benign
0.61
T;T;T
MetaRNN
Benign
0.0018
T;T;T
MetaSVM
Benign
-1.1
T
PROVEAN
Benign
-1.7
N;D;D
REVEL
Benign
0.016
Sift
Benign
0.041
D;D;T
Sift4G
Benign
0.34
T;T;.
Polyphen
0.012
B;.;.
Vest4
0.079
MutPred
0.26
Gain of catalytic residue at L198 (P = 0.0212);.;.;
MPC
0.074
ClinPred
0.00095
T
GERP RS
0.43
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.17
gMVP
0.048

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs115430352; hg19: chr11-557617; API