chr6-54167063-T-C

Variant names:

• chr6-54167063-T-C
• rs1280858
• NM_001281747.2:c.2500-2465T>C

Variant summary

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

The NM_001281747.2(MLIP):​c.2500-2465T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 151,966 control chromosomes in the GnomAD database, including 67,856 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 0.94 (67856 hom., cov: 32)
• Consequence: MLIP NM_001281747.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• Publications: 1 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

LOC105375097 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 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.2500-2465T>C		intron	N/A	NP_001268676.1
	MLIP	NM_001281746.2		c.2467-2465T>C		intron	N/A	NP_001268675.1
	MLIP	NM_138569.3		c.895-2465T>C		intron	N/A	NP_612636.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLIP	ENST00000502396.6	TSL:2 MANE Select	c.2500-2465T>C		intron	N/A	ENSP00000426290.1
	MLIP	ENST00000514921.5	TSL:1	c.2467-2465T>C		intron	N/A	ENSP00000425142.1
	MLIP	ENST00000370876.6	TSL:1	c.427-2465T>C		intron	N/A	ENSP00000359913.2

Frequencies

GnomAD3 genomes AF: 0.941 AC: 142898 AN: 151848 Hom.: 67813 Cov.: 32

Gnomad AFR AF: 0.803

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.973

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.974

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.959

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

GnomAD4 genome AF: 0.941 AC: 142998 AN: 151966 Hom.: 67856 Cov.: 32 AF XY: 0.943 AC XY: 70046 AN XY: 74316

African (AFR) AF: 0.803 AC: 33301 AN: 41470

American (AMR) AF: 0.973 AC: 14809 AN: 15222

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3466 AN: 3466

East Asian (EAS) AF: 0.988 AC: 5083 AN: 5144

South Asian (SAS) AF: 0.974 AC: 4702 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10618 AN: 10622

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67799 AN: 67904

Other (OTH) AF: 0.960 AC: 2021 AN: 2106

Alfa AF: 0.972 Hom.: 3966

Bravo AF: 0.934

Asia WGS AF: 0.967 AC: 3362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.2
DANN	Benign	0.44
PhyloP100		-0.042
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: rs1280858; hg19: chr6-54031861;