rs115430352

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-557617-C-A
• chr11-557617-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_173573.3(LMNTD2):​c.579G>T​(p.Met193Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000779 in 1,613,232 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00083 (2 hom.)
• Consequence: LMNTD2 NM_173573.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.035343975).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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

Frequencies

GnomAD3 genomes AF: 0.000322 AC: 49 AN: 152180 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000260 AC: 65 AN: 250348 AF XY: 0.000236

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000496

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000826 AC: 1207 AN: 1460934 Hom.: 2 Cov.: 36 AF XY: 0.000795 AC XY: 578 AN XY: 726748

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.000201 AC: 9 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52672

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00105 AC: 1163 AN: 1111840

Other (OTH) AF: 0.000497 AC: 30 AN: 60360

GnomAD4 genome AF: 0.000322 AC: 49 AN: 152298 Hom.: 0 Cov.: 33 AF XY: 0.000376 AC XY: 28 AN XY: 74480

African (AFR) AF: 0.000120 AC: 5 AN: 41550

American (AMR) AF: 0.000261 AC: 4 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68024

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00000436 Hom.: 193

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000778 AC: 3

ExAC AF: 0.000222 AC: 27

EpiCase AF: 0.000491

EpiControl AF: 0.000415

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	Uncertain	0.45
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.043	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.46
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.015
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)
MVP		0.26
MPC		0.074
ClinPred		0.032	T
GERP RS		0.43
Varity_R		0.17
gMVP		0.048
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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;