12-25546545-G-T

Position:

• chr12-25546545-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145728.2(LMNTD1):​c.320C>A​(p.Pro107His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,381,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: LMNTD1 NM_001145728.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.714

Genes affected

LMNTD1 (HGNC:26683): (lamin tail domain containing 1) Predicted to act upstream of or within cell population proliferation. Predicted to be located in nucleus. Predicted to be active in cytoplasm and nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

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=0.07214722).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMNTD1	NM_001145728.2	c.320C>A	p.Pro107His	missense_variant	4/10	ENST00000458174.7	NP_001139200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMNTD1	ENST00000458174.7	c.320C>A	p.Pro107His	missense_variant	4/10	2	NM_001145728.2	ENSP00000407353	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000217 AC: 3 AN: 1381834 Hom.: 0 Cov.: 30 AF XY: 0.00000292 AC XY: 2 AN XY: 685070

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000187

Gnomad4 OTH exome AF: 0.0000177

GnomAD4 genome Cov.: 32

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

Jun 06, 2023

The c.320C>A (p.P107H) alteration is located in exon 4 (coding exon 3) of the LMNTD1 gene. This alteration results from a C to A substitution at nucleotide position 320, causing the proline (P) at amino acid position 107 to be replaced by a histidine (H). 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	0.078
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.52
DANN	Benign	0.94
DEOGEN2	Benign	0.011	T;.;.;.;T;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.61	T;T;T;T;T;T;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.072	T;T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.93	N;N;N;N;N;N;N
REVEL	Benign	0.043
Sift	Benign	0.056	T;D;D;D;T;T;D
Sift4G	Benign	0.30	T;T;T;T;.;.;.
Polyphen		0.0010	B;B;B;B;.;.;.
Vest4		0.081
MutPred		0.28		Gain of loop (P = 0.0097);.;.;.;.;.;.;
MVP		0.040
MPC		0.30
ClinPred		0.037	T
GERP RS		-3.9
Varity_R		0.045
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-25699479;