11-555317-T-G

Variant names:

• chr11-555317-T-G
• rs143504198
• NM_173573.3:c.1761A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173573.3(LMNTD2):​c.1761A>C​(p.Glu587Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: LMNTD2 NM_173573.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500

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]

ACMG classification

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=0.09110111).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMNTD2	NM_173573.3	c.1761A>C	p.Glu587Asp	missense_variant	Exon 13 of 14	ENST00000329451.8	NP_775844.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMNTD2	ENST00000329451.8	c.1761A>C	p.Glu587Asp	missense_variant	Exon 13 of 14	1	NM_173573.3	ENSP00000331167.3
LMNTD2	ENST00000469990.1	n.963A>C		non_coding_transcript_exon_variant	Exon 3 of 4	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000119 AC: 1 AN: 83834 Hom.: 0 AF XY: 0.0000214 AC XY: 1 AN XY: 46764

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000181

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 Cov.: 32

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000859 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.35	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.11
Sift	Benign	0.10	T
Sift4G	Benign	0.25	T
Polyphen		0.99	D
Vest4		0.26
MutPred		0.18		Loss of sheet (P = 0.0181);
MVP		0.30
MPC		0.095
ClinPred		0.12	T
GERP RS		3.0
Varity_R		0.068
gMVP		0.039

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

Other links and lift over

dbSNP: rs143504198; hg19: chr11-555317;