chr11-558629-C-T

Variant names:

• chr11-558629-C-T
• NM_173573.3:c.296G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173573.3(LMNTD2):​c.296G>A​(p.Gly99Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,454,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LMNTD2 NM_173573.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.982
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15970907).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173573.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMNTD2	NM_173573.3	MANE Select	c.296G>A	p.Gly99Glu	missense	Exon 3 of 14	NP_775844.2	Q8IXW0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMNTD2	ENST00000329451.8	TSL:1 MANE Select	c.296G>A	p.Gly99Glu	missense	Exon 3 of 14	ENSP00000331167.3	Q8IXW0
	LMNTD2	ENST00000886189.1		c.296G>A	p.Gly99Glu	missense	Exon 3 of 14	ENSP00000556248.1
	LMNTD2	ENST00000886190.1		c.314G>A	p.Gly105Glu	missense	Exon 3 of 14	ENSP00000556249.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1454612 Hom.: 0 Cov.: 46 AF XY: 0.00000138 AC XY: 1 AN XY: 723030

African (AFR) AF: 0.00 AC: 0 AN: 33370

American (AMR) AF: 0.00 AC: 0 AN: 44330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26022

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39554

South Asian (SAS) AF: 0.00 AC: 0 AN: 85392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4210

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110100

Other (OTH) AF: 0.00 AC: 0 AN: 59992

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.98
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.13
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.45
MutPred		0.34		Gain of disorder (P = 0.0404)
MVP		0.37
MPC		0.44
ClinPred		0.72	D
GERP RS		2.0
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.8
Varity_R		0.20
gMVP		0.089
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

hg19: chr11-558629;