chr12-25507645-A-G

Variant names:

• chr12-25507645-A-G
• rs10743565
• NM_001145728.2:c.1190-3845T>C

Variant summary

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

The NM_001145728.2(LMNTD1):​c.1190-3845T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 152,054 control chromosomes in the GnomAD database, including 33,108 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (33108 hom., cov: 31)
• Consequence: LMNTD1 NM_001145728.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145728.2. 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
	LMNTD1	NM_001145728.2	MANE Select	c.1190-3845T>C		intron	N/A	NP_001139200.1	Q8N9Z9-5
	LMNTD1	NM_152590.3		c.1127-3845T>C		intron	N/A	NP_689803.2	Q8N9Z9-1
	LMNTD1	NM_001145729.1		c.1070-3845T>C		intron	N/A	NP_001139201.1	Q8N9Z9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMNTD1	ENST00000458174.7	TSL:2 MANE Select	c.1190-3845T>C		intron	N/A	ENSP00000407353.2	Q8N9Z9-5
	LMNTD1	ENST00000413632.6	TSL:1	c.1070-3845T>C		intron	N/A	ENSP00000393150.2	Q8N9Z9-4
	LMNTD1	ENST00000539744.5	TSL:1	c.836-3845T>C		intron	N/A	ENSP00000443132.1	Q8N9Z9-2

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99585 AN: 151936 Hom.: 33083 Cov.: 31

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.664

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.655 AC: 99660 AN: 152054 Hom.: 33108 Cov.: 31 AF XY: 0.655 AC XY: 48655 AN XY: 74314

African (AFR) AF: 0.556 AC: 23035 AN: 41462

American (AMR) AF: 0.680 AC: 10411 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1924 AN: 3466

East Asian (EAS) AF: 0.650 AC: 3354 AN: 5160

South Asian (SAS) AF: 0.604 AC: 2911 AN: 4816

European-Finnish (FIN) AF: 0.682 AC: 7197 AN: 10548

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48447 AN: 67980

Other (OTH) AF: 0.663 AC: 1402 AN: 2116

Alfa AF: 0.687 Hom.: 13760

Bravo AF: 0.651

Asia WGS AF: 0.655 AC: 2277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.023
DANN	Benign	0.41
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs10743565; hg19: chr12-25660579;