11-558660-G-A

Variant names:

• chr11-558660-G-A
• rs146543744
• NM_173573.3:c.265C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_173573.3(LMNTD2):​c.265C>T​(p.Arg89Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,605,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R89G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: LMNTD2 NM_173573.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112
• Publications: 0 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08368349).

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.265C>T	p.Arg89Trp	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.265C>T	p.Arg89Trp	missense	Exon 3 of 14	ENSP00000331167.3	Q8IXW0
	LMNTD2	ENST00000886189.1		c.265C>T	p.Arg89Trp	missense	Exon 3 of 14	ENSP00000556248.1
	LMNTD2	ENST00000886190.1		c.283C>T	p.Arg95Trp	missense	Exon 3 of 14	ENSP00000556249.1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152234 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000340 AC: 8 AN: 235050 AF XY: 0.0000313

Gnomad AFR exome AF: 0.000205

Gnomad AMR exome AF: 0.0000602

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000569

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000190

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000145 AC: 21 AN: 1453120 Hom.: 0 Cov.: 45 AF XY: 0.0000180 AC XY: 13 AN XY: 722296

African (AFR) AF: 0.000120 AC: 4 AN: 33334

American (AMR) AF: 0.0000456 AC: 2 AN: 43890

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25958

East Asian (EAS) AF: 0.0000507 AC: 2 AN: 39412

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84952

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4580

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1109478

Other (OTH) AF: 0.00 AC: 0 AN: 59956

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152234 Hom.: 0 Cov.: 34 AF XY: 0.0000672 AC XY: 5 AN XY: 74370

African (AFR) AF: 0.000241 AC: 10 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000248 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-0.92	T
PhyloP100		0.11
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.042	B
Vest4		0.32
MutPred		0.51		Gain of loop (P = 0.0045)
MVP		0.14
MPC		0.067
ClinPred		0.071	T
GERP RS		1.9
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.2
Varity_R		0.10
gMVP		0.30
Mutation Taster		=99/1	polymorphism

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: rs146543744; hg19: chr11-558660;