6-54190039-A-T

Variant names:

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

Variant summary

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

The NM_001281747.2(MLIP):​c.2589+125A>T 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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

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

LOC124901335 (HGNC:):

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=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLIP	NM_001281747.2	c.2589+125A>T		intron_variant	Intron 10 of 13	ENST00000502396.6	NP_001268676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLIP	ENST00000502396.6	c.2589+125A>T		intron_variant	Intron 10 of 13	2	NM_001281747.2	ENSP00000426290.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 525804 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 277320

African (AFR) AF: 0.00 AC: 0 AN: 13470

American (AMR) AF: 0.00 AC: 0 AN: 16850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14840

East Asian (EAS) AF: 0.00 AC: 0 AN: 30048

South Asian (SAS) AF: 0.00 AC: 0 AN: 40342

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34690

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2182

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 345500

Other (OTH) AF: 0.00 AC: 0 AN: 27882

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 3344

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.3
DANN	Benign	0.81
PhyloP100		0.52

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;