11-558713-C-T

Variant names:

• chr11-558713-C-T
• rs148047813
• NM_173573.3:c.212G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_173573.3(LMNTD2):​c.212G>A​(p.Arg71Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000305 in 1,606,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R71P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: LMNTD2 NM_173573.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.363
• Publications: 4 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.036952317).

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.212G>A	p.Arg71Gln	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.212G>A	p.Arg71Gln	missense	Exon 3 of 14	ENSP00000331167.3	Q8IXW0
	LMNTD2	ENST00000886189.1		c.212G>A	p.Arg71Gln	missense	Exon 3 of 14	ENSP00000556248.1
	LMNTD2	ENST00000886190.1		c.230G>A	p.Arg77Gln	missense	Exon 3 of 14	ENSP00000556249.1

Frequencies

GnomAD3 genomes AF: 0.0000722 AC: 11 AN: 152266 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000255 AC: 6 AN: 235276 AF XY: 0.0000234

Gnomad AFR exome AF: 0.000205

Gnomad AMR exome AF: 0.0000302

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000190

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000261 AC: 38 AN: 1454356 Hom.: 0 Cov.: 46 AF XY: 0.0000318 AC XY: 23 AN XY: 723112

African (AFR) AF: 0.000360 AC: 12 AN: 33354

American (AMR) AF: 0.0000228 AC: 1 AN: 43784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25972

East Asian (EAS) AF: 0.00 AC: 0 AN: 39420

South Asian (SAS) AF: 0.00 AC: 0 AN: 85282

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51654

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5312

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1109538

Other (OTH) AF: 0.0000333 AC: 2 AN: 60040

GnomAD4 genome AF: 0.0000722 AC: 11 AN: 152384 Hom.: 0 Cov.: 33 AF XY: 0.0000805 AC XY: 6 AN XY: 74516

African (AFR) AF: 0.000240 AC: 10 AN: 41602

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000574 Hom.: 0

Bravo AF: 0.000117

ESP6500AA AF: 0.000455 AC: 2

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000414 AC: 5

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	Benign	0.24
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.36
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.066
Sift	Benign	0.092	T
Sift4G	Benign	0.20	T
Polyphen		0.90	P
Vest4		0.34
MVP		0.33
MPC		0.42
ClinPred		0.036	T
GERP RS		2.0
Varity_R		0.13
gMVP		0.32
Mutation Taster		=100/0	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: rs148047813; hg19: chr11-558713; COSMIC: COSV99051800; COSMIC: COSV99051800;