rs1853007415

Variant names:

• chr11-557985-T-A
• rs1853007415
• NM_173573.3:c.454A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-557985-T-A
• chr11-557985-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173573.3(LMNTD2):​c.454A>T​(p.Met152Leu) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M152V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LMNTD2 NM_173573.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.023697883).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMNTD2	NM_173573.3	c.454A>T	p.Met152Leu	missense_variant	Exon 5 of 14	ENST00000329451.8	NP_775844.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMNTD2	ENST00000329451.8	c.454A>T	p.Met152Leu	missense_variant	Exon 5 of 14	1	NM_173573.3	ENSP00000331167.3
LMNTD2	ENST00000441853.5	c.475A>T	p.Met159Leu	missense_variant	Exon 6 of 9	3		ENSP00000393529.1
LMNTD2	ENST00000486629.1	c.484A>T	p.Met162Leu	missense_variant	Exon 5 of 7	5		ENSP00000435529.1
LMNTD2-AS1	ENST00000527620.5	n.391T>A		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.2
DANN	Benign	0.50
DEOGEN2	Benign	0.0064	T;T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.40	T;T;T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.024	T;T;T
MetaSVM	Benign	-0.98	T
PROVEAN	Benign	0.68	N;N;N
REVEL	Benign	0.024
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;.
Polyphen		0.0	B;.;.
Vest4		0.12
MutPred		0.27		Gain of phosphorylation at T148 (P = 0.286);.;.;
MVP		0.14
MPC		0.061
ClinPred		0.030	T
GERP RS		-2.7
Varity_R		0.087
gMVP		0.020

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: rs1853007415; hg19: chr11-557985;