Variant 11-557985-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_173573.3(LMNTD2):c.454A>G(p.Met152Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000484 in 1,447,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

LMNTD2
NM_173573.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.320

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 links:

LMNTD2-AS1 (HGNC:):

LMNTD2-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038553834).

BP6

Variant 11-557985-T-C is Benign according to our data. Variant chr11-557985-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2604590.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMNTD2	NM_173573.3 linkuse as main transcript	c.454A>G	p.Met152Val	missense_variant	5/14	ENST00000329451.8	NP_775844.2	Q8IXW0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LMNTD2	ENST00000329451.8 linkuse as main transcript	c.454A>G	p.Met152Val	missense_variant	5/14	1	NM_173573.3	ENSP00000331167.3	Q8IXW0
LMNTD2	ENST00000441853.5 linkuse as main transcript	c.475A>G	p.Met159Val	missense_variant	6/9	3		ENSP00000393529.1	C9JV74
LMNTD2	ENST00000486629.1 linkuse as main transcript	c.484A>G	p.Met162Val	missense_variant	5/7	5		ENSP00000435529.1	E9PJR3
LMNTD2-AS1	ENST00000527620.5 linkuse as main transcript	n.391T>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000484

AC:

AN:

1447666

Hom.:

Cov.:

AF XY:

0.00000557

AC XY:

AN XY:

718408

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:

0.00000634

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000318

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

2.6

DANN

Benign

0.29

DEOGEN2

Benign

0.013

T;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.36

T;T;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.039

T;T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.62

N;N;N

REVEL

Benign

0.033

Sift

Benign

0.15

T;T;T

Sift4G

Benign

0.18

T;T;.

Polyphen

0.0

B;.;.

Vest4

0.095

MutPred

0.22

Loss of catalytic residue at M152 (P = 0.1416);.;.;

MVP

0.18

MPC

0.066

ClinPred

0.026

GERP RS

-2.7

Varity_R

0.058

gMVP

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over