Variant 12-25520038-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001145728.2(LMNTD1):c.836C>T(p.Ala279Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 28)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

LMNTD1
NM_001145728.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.335

Variant links:

Genes affected

LMNTD1 (HGNC:26683): (lamin tail domain containing 1) Predicted to act upstream of or within cell population proliferation. Predicted to be located in nucleus. Predicted to be active in cytoplasm and nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

LMNTD1 links:

LMNTD1 (HGNC:):

LMNTD1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09638396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMNTD1	NM_001145728.2 linkuse as main transcript	c.836C>T	p.Ala279Val	missense_variant	7/10	ENST00000458174.7	NP_001139200.1	Q8N9Z9-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMNTD1	ENST00000458174.7 linkuse as main transcript	c.836C>T	p.Ala279Val	missense_variant	7/10	2	NM_001145728.2	ENSP00000407353.2		Q8N9Z9-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251308

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461344

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727012

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000224

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2023

The c.836C>T (p.A279V) alteration is located in exon 7 (coding exon 6) of the LMNTD1 gene. This alteration results from a C to T substitution at nucleotide position 836, causing the alanine (A) at amino acid position 279 to be replaced by a valine (V). 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

0.14

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.029

T;.;.;.;.;.

Eigen

Benign

-0.097

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.84

T;T;T;T;T;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.096

T;T;T;T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.9

N;N;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.14

T;T;T;T;T;T

Sift4G

Pathogenic

0.0

D;D;D;D;D;.

Polyphen

0.91

P;.;D;P;D;.

Vest4

0.12

MutPred

0.38

Gain of catalytic residue at I253 (P = 0.0022);.;.;.;.;.;

MVP

0.18

MPC

0.38

ClinPred

0.093

GERP RS

4.2

Varity_R

0.074

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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