Genetic Variant NM_173573.3:c.1761A>G (chr11-555317-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_173573.3(LMNTD2):c.1761A>G(p.Glu587Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00782 in 1,418,240 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0085 ( 12 hom., cov: 31)

Exomes 𝑓: 0.0077 ( 45 hom. )

Consequence

LMNTD2
NM_173573.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00500

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 11-555317-T-C is Benign according to our data. Variant chr11-555317-T-C is described in ClinVar as [Benign]. Clinvar id is 2641070.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.005 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMNTD2	NM_173573.3 link	c.1761A>G	p.Glu587Glu	synonymous_variant	Exon 13 of 14	ENST00000329451.8	NP_775844.2	Q8IXW0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMNTD2	ENST00000329451.8 link	c.1761A>G	p.Glu587Glu	synonymous_variant	Exon 13 of 14	1	NM_173573.3	ENSP00000331167.3		Q8IXW0
LMNTD2	ENST00000469990.1 link	n.963A>G		non_coding_transcript_exon_variant	Exon 3 of 4	1

Frequencies

GnomAD3 genomes

AF:

0.00841

AC:

1275

AN:

151534

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00940

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0131

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.000584

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00548

Gnomad MID

AF:

0.00323

Gnomad NFE

AF:

0.00867

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00588

AC:

493

AN:

83834

Hom.:

AF XY:

0.00577

AC XY:

270

AN XY:

46764

show subpopulations

Gnomad AFR exome

AF:

0.00782

Gnomad AMR exome

AF:

0.00772

Gnomad ASJ exome

AF:

0.00158

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00423

Gnomad NFE exome

AF:

0.00700

Gnomad OTH exome

AF:

0.00946

GnomAD4 exome

AF:

0.00774

AC:

9805

AN:

1266600

Hom.:

Cov.:

AF XY:

0.00744

AC XY:

4590

AN XY:

616554

show subpopulations

Gnomad4 AFR exome

AF:

0.00918

Gnomad4 AMR exome

AF:

0.00884

Gnomad4 ASJ exome

AF:

0.00441

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000345

Gnomad4 FIN exome

AF:

0.00546

Gnomad4 NFE exome

AF:

0.00855

Gnomad4 OTH exome

AF:

0.00737

GnomAD4 genome

AF:

0.00845

AC:

1282

AN:

151640

Hom.:

Cov.:

AF XY:

0.00808

AC XY:

599

AN XY:

74142

show subpopulations

Gnomad4 AFR

AF:

0.00954

Gnomad4 AMR

AF:

0.0130

Gnomad4 ASJ

AF:

0.00433

Gnomad4 EAS

AF:

0.000586

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00548

Gnomad4 NFE

AF:

0.00867

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00707

Hom.:

Bravo

AF:

0.00956

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

LMNTD2: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.8

DANN

Benign

0.61

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