NM_173573.3:c.1761A>C

Variant names:

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

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.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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E587E) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: LMNTD2 NM_173573.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 2 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]

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=0.09110111).

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.1761A>C	p.Glu587Asp	missense	Exon 13 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.1761A>C	p.Glu587Asp	missense	Exon 13 of 14	ENSP00000331167.3	Q8IXW0
	LMNTD2	ENST00000469990.1	TSL:1	n.963A>C		non_coding_transcript_exon	Exon 3 of 4
	LMNTD2	ENST00000886189.1		c.1776A>C	p.Glu592Asp	missense	Exon 13 of 14	ENSP00000556248.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000119 AC: 1 AN: 83834 AF XY: 0.0000214

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 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 v4.9

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
PhyloP100		-0.0050
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
Mutation Taster		=98/2	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

dbSNP: rs143504198; hg19: chr11-555317;