6-54190039-A-G

Variant names:

• chr6-54190039-A-G
• rs9296739
• NM_001281747.2:c.2589+125A>G

Variant summary

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

The NM_001281747.2(MLIP):​c.2589+125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 676,212 control chromosomes in the GnomAD database, including 133,064 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 0.55 (24755 hom., cov: 32)
  • Exomes 𝑓: 0.64 (108309 hom.)
• Consequence: MLIP NM_001281747.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.524
• Publications: 4 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

LOC124901335 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.67 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.2589+125A>G		intron	N/A	NP_001268676.1	Q5VWP3-3
	MLIP	NM_001281746.2		c.2556+125A>G		intron	N/A	NP_001268675.1	Q5VWP3-4
	MLIP	NM_138569.3		c.984+125A>G		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.2589+125A>G		intron	N/A	ENSP00000426290.1	Q5VWP3-3
	MLIP	ENST00000514921.5	TSL:1	c.2556+125A>G		intron	N/A	ENSP00000425142.1	Q5VWP3-4
	MLIP	ENST00000370876.6	TSL:1	c.516+125A>G		intron	N/A	ENSP00000359913.2	Q5VWP3-2

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83175 AN: 151872 Hom.: 24763 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.579

GnomAD4 exome AF: 0.638 AC: 334599 AN: 524224 Hom.: 108309 AF XY: 0.641 AC XY: 177286 AN XY: 276450

African (AFR) AF: 0.292 AC: 3925 AN: 13432

American (AMR) AF: 0.487 AC: 8186 AN: 16804

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 9567 AN: 14806

East Asian (EAS) AF: 0.660 AC: 19771 AN: 29954

South Asian (SAS) AF: 0.681 AC: 27347 AN: 40160

European-Finnish (FIN) AF: 0.702 AC: 24314 AN: 34612

Middle Eastern (MID) AF: 0.594 AC: 1293 AN: 2176

European-Non Finnish (NFE) AF: 0.648 AC: 223058 AN: 344462

Other (OTH) AF: 0.616 AC: 17138 AN: 27818

GnomAD4 genome AF: 0.547 AC: 83161 AN: 151988 Hom.: 24755 Cov.: 32 AF XY: 0.555 AC XY: 41207 AN XY: 74286

African (AFR) AF: 0.297 AC: 12325 AN: 41438

American (AMR) AF: 0.508 AC: 7764 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2274 AN: 3472

East Asian (EAS) AF: 0.688 AC: 3553 AN: 5168

South Asian (SAS) AF: 0.689 AC: 3315 AN: 4808

European-Finnish (FIN) AF: 0.722 AC: 7623 AN: 10562

Middle Eastern (MID) AF: 0.613 AC: 179 AN: 292

European-Non Finnish (NFE) AF: 0.652 AC: 44269 AN: 67948

Other (OTH) AF: 0.573 AC: 1208 AN: 2108

Alfa AF: 0.574 Hom.: 3344

Bravo AF: 0.518

Asia WGS AF: 0.661 AC: 2293 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.8
DANN	Benign	0.77
PhyloP100		0.52
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: rs9296739; hg19: chr6-54054837;