6-54105520-T-G

Variant names:

• chr6-54105520-T-G
• rs545829
• ENST00000514921.5:c.64-15927T>G

Variant summary

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

The NM_001281746.2(MLIP):​c.64-15927T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,070 control chromosomes in the GnomAD database, including 12,102 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 0.39 (12102 hom., cov: 32)
• Consequence: MLIP NM_001281746.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 5 publications found

Genes affected

MLIP (HGNC:21355): (muscular LMNA interacting protein) Predicted to enable lamin binding activity and transcription corepressor activity. Predicted to be involved in negative regulation of cardiac muscle hypertrophy in response to stress; negative regulation of transcription by RNA polymerase II; and positive regulation of transcription by RNA polymerase II. Predicted to be located in nuclear lumen. Predicted to be active in PML body; nuclear envelope; and sarcolemma. [provided by Alliance of Genome Resources, Apr 2022]

MLIP Gene-Disease associations (from GenCC):

• myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001281746.2. 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
	MLIP	NM_001281746.2		c.64-15927T>G		intron	N/A	NP_001268675.1	Q5VWP3-4
	MLIP	NM_138569.3		c.64-15927T>G		intron	N/A	NP_612636.2	Q5VWP3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLIP	ENST00000514921.5	TSL:1	c.64-15927T>G		intron	N/A	ENSP00000425142.1	Q5VWP3-4
	MLIP	ENST00000370876.6	TSL:1	c.34-18953T>G		intron	N/A	ENSP00000359913.2	Q5VWP3-2
	MLIP	ENST00000274897.9	TSL:2	c.64-15927T>G		intron	N/A	ENSP00000274897.5	Q5VWP3-1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59333 AN: 151952 Hom.: 12065 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.391 AC: 59431 AN: 152070 Hom.: 12102 Cov.: 32 AF XY: 0.386 AC XY: 28666 AN XY: 74348

African (AFR) AF: 0.497 AC: 20611 AN: 41456

American (AMR) AF: 0.462 AC: 7061 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1156 AN: 3472

East Asian (EAS) AF: 0.301 AC: 1557 AN: 5178

South Asian (SAS) AF: 0.286 AC: 1378 AN: 4822

European-Finnish (FIN) AF: 0.284 AC: 3007 AN: 10594

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23497 AN: 67964

Other (OTH) AF: 0.378 AC: 798 AN: 2112

Alfa AF: 0.386 Hom.: 2022

Bravo AF: 0.411

Asia WGS AF: 0.303 AC: 1056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.17
DANN	Benign	0.49
PhyloP100		-1.5
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: rs545829; hg19: chr6-53970318;