chr6-54149122-C-T

Position:

• chr6-54149122-C-T

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001281747.2(MLIP):​c.2284C>T​(p.Gln762Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000274 in 1,460,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: MLIP NM_001281747.2 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.43

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]

LOC105375097 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 6-54149122-C-T is Pathogenic according to our data. Variant chr6-54149122-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 1801327.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-54149122-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLIP	NM_001281747.2	c.2284C>T	p.Gln762Ter	stop_gained	5/14	ENST00000502396.6	NP_001268676.1
LOC105375097	XR_001744172.2	n.141-1539G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLIP	ENST00000502396.6	c.2284C>T	p.Gln762Ter	stop_gained	5/14	2	NM_001281747.2	ENSP00000426290

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460074 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726382

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.61	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	45
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.97
FATHMM_MKL	Uncertain	0.94	D
MutationTaster	Benign	1.0	A;A;A;D;D;D;D
Vest4		0.41
GERP RS		5.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.21		Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-54013920;