NM_001281747.2:c.391C>G

Variant names:

• chr6-54124611-C-G
• rs764062611
• NM_001281747.2:c.391C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001281747.2(MLIP):​c.391C>G​(p.Gln131Glu) variant causes a missense 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q131K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MLIP NM_001281747.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.10
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28541738).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001281747.2. 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_001281747.2	MANE Select	c.391C>G	p.Gln131Glu	missense	Exon 3 of 14	NP_001268676.1	Q5VWP3-3
	MLIP	NM_001281746.2		c.358C>G	p.Gln120Glu	missense	Exon 3 of 12	NP_001268675.1	Q5VWP3-4
	MLIP	NM_138569.3		c.358C>G	p.Gln120Glu	missense	Exon 3 of 13	NP_612636.2	Q5VWP3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLIP	ENST00000502396.6	TSL:2 MANE Select	c.391C>G	p.Gln131Glu	missense	Exon 3 of 14	ENSP00000426290.1	Q5VWP3-3
	MLIP	ENST00000514921.5	TSL:1	c.358C>G	p.Gln120Glu	missense	Exon 3 of 12	ENSP00000425142.1	Q5VWP3-4
	MLIP	ENST00000370876.6	TSL:1	c.172C>G	p.Gln58Glu	missense	Exon 2 of 7	ENSP00000359913.2	Q5VWP3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.046	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.1
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.10
Sift	Uncertain	0.0070	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.084	B
Vest4		0.50
MutPred		0.43		Gain of sheet (P = 0.0827)
MVP		0.088
MPC		0.017
ClinPred		0.83	D
GERP RS		4.8
Varity_R		0.25
gMVP		0.22
Mutation Taster		=82/18	polymorphism

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: rs764062611; hg19: chr6-53989409;