11-557617-C-T

Variant names:

• chr11-557617-C-T
• rs115430352
• NM_173573.3:c.579G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173573.3(LMNTD2):​c.579G>A​(p.Met193Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 1,613,194 control chromosomes in the GnomAD database, including 1,311 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.037 (108 hom., cov: 33)
  • Exomes 𝑓: 0.038 (1203 hom.)
• Consequence: LMNTD2 NM_173573.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.459
• Publications: 18 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018461645).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0839 is higher than 0.05.

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.579G>A	p.Met193Ile	missense	Exon 6 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.579G>A	p.Met193Ile	missense	Exon 6 of 14	ENSP00000331167.3	Q8IXW0
	LMNTD2	ENST00000886189.1		c.594G>A	p.Met198Ile	missense	Exon 6 of 14	ENSP00000556248.1
	LMNTD2	ENST00000886190.1		c.612G>A	p.Met204Ile	missense	Exon 6 of 14	ENSP00000556249.1

Frequencies

GnomAD3 genomes AF: 0.0369 AC: 5617 AN: 152170 Hom.: 108 Cov.: 33

Gnomad AFR AF: 0.0302

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0329

Gnomad ASJ AF: 0.0521

Gnomad EAS AF: 0.00597

Gnomad SAS AF: 0.0300

Gnomad FIN AF: 0.0624

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0397

Gnomad OTH AF: 0.0388

GnomAD2 exomes AF: 0.0371 AC: 9293 AN: 250348 AF XY: 0.0381

Gnomad AFR exome AF: 0.0289

Gnomad AMR exome AF: 0.0247

Gnomad ASJ exome AF: 0.0509

Gnomad EAS exome AF: 0.00604

Gnomad FIN exome AF: 0.0622

Gnomad NFE exome AF: 0.0407

Gnomad OTH exome AF: 0.0467

GnomAD4 exome AF: 0.0383 AC: 56003 AN: 1460906 Hom.: 1203 Cov.: 36 AF XY: 0.0386 AC XY: 28047 AN XY: 726728

African (AFR) AF: 0.0300 AC: 1004 AN: 33480

American (AMR) AF: 0.0264 AC: 1180 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0534 AC: 1395 AN: 26136

East Asian (EAS) AF: 0.00539 AC: 214 AN: 39700

South Asian (SAS) AF: 0.0367 AC: 3162 AN: 86258

European-Finnish (FIN) AF: 0.0643 AC: 3384 AN: 52668

Middle Eastern (MID) AF: 0.0904 AC: 521 AN: 5766

European-Non Finnish (NFE) AF: 0.0383 AC: 42606 AN: 1111818

Other (OTH) AF: 0.0420 AC: 2537 AN: 60360

GnomAD4 genome AF: 0.0369 AC: 5625 AN: 152288 Hom.: 108 Cov.: 33 AF XY: 0.0379 AC XY: 2825 AN XY: 74476

African (AFR) AF: 0.0302 AC: 1256 AN: 41548

American (AMR) AF: 0.0329 AC: 503 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0521 AC: 181 AN: 3472

East Asian (EAS) AF: 0.00598 AC: 31 AN: 5180

South Asian (SAS) AF: 0.0298 AC: 144 AN: 4828

European-Finnish (FIN) AF: 0.0624 AC: 663 AN: 10622

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0397 AC: 2701 AN: 68018

Other (OTH) AF: 0.0393 AC: 83 AN: 2112

Alfa AF: 0.0365 Hom.: 193

Bravo AF: 0.0353

TwinsUK AF: 0.0399 AC: 148

ALSPAC AF: 0.0355 AC: 137

ESP6500AA AF: 0.0284 AC: 125

ESP6500EA AF: 0.0408 AC: 351

ExAC AF: 0.0374 AC: 4535

EpiCase AF: 0.0463

EpiControl AF: 0.0446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.043	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.46
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.016
Sift	Benign	0.041	D
Sift4G	Benign	0.34	T
Polyphen		0.012	B
Vest4		0.079
MutPred		0.26		Gain of catalytic residue at L198 (P = 0.0212)
MPC		0.074
ClinPred		0.00095	T
GERP RS		0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.048
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs115430352; hg19: chr11-557617;