rs665640

Variant names:

• chr6-54122584-T-A
• rs665640
• NM_001281747.2:c.252+982T>A

Variant summary

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

The NM_001281747.2(MLIP):​c.252+982T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,050 control chromosomes in the GnomAD database, including 11,602 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 (11602 hom., cov: 32)
• Consequence: MLIP NM_001281747.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409
• Publications: 3 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

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.252+982T>A		intron	N/A	NP_001268676.1	Q5VWP3-3
	MLIP	NM_001281746.2		c.219+982T>A		intron	N/A	NP_001268675.1	Q5VWP3-4
	MLIP	NM_138569.3		c.219+982T>A		intron	N/A	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.252+982T>A		intron	N/A	ENSP00000426290.1	Q5VWP3-3
	MLIP	ENST00000514921.5	TSL:1	c.219+982T>A		intron	N/A	ENSP00000425142.1	Q5VWP3-4
	MLIP	ENST00000370876.6	TSL:1	c.34-1889T>A		intron	N/A	ENSP00000359913.2	Q5VWP3-2

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58596 AN: 151932 Hom.: 11577 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.386 AC: 58674 AN: 152050 Hom.: 11602 Cov.: 32 AF XY: 0.380 AC XY: 28273 AN XY: 74334

African (AFR) AF: 0.454 AC: 18825 AN: 41438

American (AMR) AF: 0.469 AC: 7160 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1249 AN: 3472

East Asian (EAS) AF: 0.300 AC: 1554 AN: 5176

South Asian (SAS) AF: 0.290 AC: 1395 AN: 4816

European-Finnish (FIN) AF: 0.284 AC: 3007 AN: 10582

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24303 AN: 67966

Other (OTH) AF: 0.381 AC: 807 AN: 2116

Alfa AF: 0.376 Hom.: 1351

Bravo AF: 0.405

Asia WGS AF: 0.301 AC: 1047 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.3
DANN	Benign	0.90
PhyloP100		0.41
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: rs665640; hg19: chr6-53987382;