11-558243-G-C

Position:

• chr11-558243-G-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.317C>G​(p.Ser106Cys) 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LMNTD2 NM_173573.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.519

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:):

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=0.09791693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMNTD2	NM_173573.3	c.317C>G	p.Ser106Cys	missense_variant	4/14	ENST00000329451.8	NP_775844.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMNTD2	ENST00000329451.8	c.317C>G	p.Ser106Cys	missense_variant	4/14	1	NM_173573.3	ENSP00000331167.3
LMNTD2	ENST00000441853.5	c.338C>G	p.Ser113Cys	missense_variant	5/9	3		ENSP00000393529.1
LMNTD2	ENST00000486629.1	c.347C>G	p.Ser116Cys	missense_variant	4/7	5		ENSP00000435529.1
LMNTD2-AS1	ENST00000527620.5	n.649G>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2021

The c.317C>G (p.S106C) alteration is located in exon 4 (coding exon 4) of the LMNTD2 gene. This alteration results from a C to G substitution at nucleotide position 317, causing the serine (S) at amino acid position 106 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.032	T;T;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.58	T;T;T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.098	T;T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-1.8	N;D;D
REVEL	Benign	0.061
Sift	Uncertain	0.018	D;D;D
Sift4G	Benign	0.072	T;T;.
Polyphen		0.99	D;.;.
Vest4		0.14
MutPred		0.16		Loss of phosphorylation at S106 (P = 0.0217);.;.;
MVP		0.24
MPC		0.35
ClinPred		0.47	T
GERP RS		0.45
Varity_R		0.090
gMVP		0.052

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: rs1589832072; hg19: chr11-558243;