6-54105520-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000514921.5(MLIP):​c.64-15927T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: MLIP ENST00000514921.5 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

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000514921.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLIP	NM_001281746.2		c.64-15927T>A		intron	N/A	NP_001268675.1
	MLIP	NM_138569.3		c.64-15927T>A		intron	N/A	NP_612636.2

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

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	0.22
PhyloP100		-1.5

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;