GeneBe

chr1-156115264-CTG-TTA

Variant names:
GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.
+1 Uncertain · Cold
-7
-6
-1
0
+5
+6
+9
+10
B
LB
VUS
LP
P
 The variant received 1 classification points (ACMG Germline Pathogenicity v2019). PM2BP7

The NM_170707.4(LMNA):c.346_348delCTGinsTTA (p.117) variant causes a synonymous change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

LMNA
NM_170707.4 synonymous

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.12

Publications

0 publications found
Variant links:
Genes affected
LMNA (HGNC:6636): (lamin A/C) The protein encoded by this gene is part of the nuclear lamina, a two-dimensional matrix of proteins located next to the inner nuclear membrane. The lamin family of proteins make up the matrix and are highly conserved in evolution. During mitosis, the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Lamin proteins are thought to be involved in nuclear stability, chromatin structure and gene expression. Vertebrate lamins consist of two types, A and B. Alternative splicing results in multiple transcript variants. Mutations in this gene lead to several diseases: Emery-Dreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease, and Hutchinson-Gilford progeria syndrome. [provided by RefSeq, May 2022]
LMNA Gene-Disease associations (from GenCC):
  • dilated cardiomyopathy 1A
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, ClinGen, G2P
  • Emery-Dreifuss muscular dystrophy 2, autosomal dominant
    Inheritance: AD, SD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • familial partial lipodystrophy, Dunnigan type
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
  • Hutchinson-Gilford progeria syndrome
    Inheritance: AD, SD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet
  • restrictive dermopathy 2
    Inheritance: AR, AD Classification: DEFINITIVE, LIMITED Submitted by: G2P
  • lipodystrophy
    Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
  • atrioventricular block
    Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
  • heart-hand syndrome, Slovenian type
    Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet
  • Charcot-Marie-Tooth disease type 2B1
    Inheritance: AR, AD Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
  • Emery-Dreifuss muscular dystrophy 3, autosomal recessive
    Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • mandibuloacral dysplasia with type A lipodystrophy
    Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
  • atrial fibrillation
    Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
  • atypical Werner syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • autosomal dominant Emery-Dreifuss muscular dystrophy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • congenital muscular dystrophy due to LMNA mutation
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • familial isolated dilated cardiomyopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • lethal restrictive dermopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • LMNA-related cardiocutaneous progeria syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • autosomal recessive Emery-Dreifuss muscular dystrophy
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • autosomal semi-dominant severe lipodystrophic laminopathy
    Inheritance: SD Classification: SUPPORTIVE Submitted by: Orphanet
  • arrhythmogenic right ventricular cardiomyopathy
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen, G2P

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_170707.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 1 points.

PM2Absent/extremely low in population databases
Absent from gnomAD (AD/XL gene) — PM2; Absent from gnomAD at well-covered site (MOI: AD+AR) (threshold 0.0001) — PM2 moderate.
BP7Synonymous variant, no splicing impact
Synonymous variant at non-conserved position with no predicted splicing impact (BP7); Synonymous at non-conserved position, no splicing concern — benign (BP7).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_170707.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

LMNA NM_170707.4
MANE Select
HGVSc / HGVSpc.346_348delCTGinsTTAp.117
Exon rankN/A
synonymous
Prot: NP_733821.1UniProt: A0A384MQX1P02545-1
LMNA NM_005572.4
MANE Plus Clinical
HGVSc / HGVSpc.346_348delCTGinsTTAp.117
Exon rankN/A
synonymous
Prot: NP_005563.1UniProt: P02545-2
LMNA NM_001406985.1
HGVSc / HGVSpc.346_348delCTGinsTTAp.117
Exon rankN/A
synonymous
Prot: NP_001393914.1

Ensembl Transcripts

LMNA ENST00000368300.9
TSL:1MANE Select
HGVSc / HGVSpc.346_348delCTGinsTTAp.117
Exon rankN/A
synonymous
Prot: ENSP00000357283.4UniProt: P02545-1
LMNA ENST00000677389.1
MANE Plus Clinical
HGVSc / HGVSpc.346_348delCTGinsTTAp.117
Exon rankN/A
synonymous
Prot: ENSP00000503633.1UniProt: P02545-2
LMNA ENST00000368299.7
TSL:1
HGVSc / HGVSpc.346_348delCTGinsTTAp.117
Exon rankN/A
synonymous
Prot: ENSP00000357282.3UniProt: P02545-6

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)
Rare (AF ≤ 0.0001 / Hom ≤ 1)
Global population databases 2 sources
GnomAD3 genomes
Cov:32
GnomAD4 genome
Cov:32
Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

PhyloP100
Uncertain4.1
Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Publications

Other links and lift over

hg19: chr1-156085055;
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