6-54019045-G-T

Variant names:

• chr6-54019045-G-T
• ENST00000514921.5:c.17G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001281746.2(MLIP):​c.17G>T​(p.Arg6Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict 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: 6.9e-7 (0 hom.)
• Consequence: MLIP NM_001281746.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.76

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-AS1 (HGNC:40963): (MLIP antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.072518855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLIP	NM_001281746.2	c.17G>T	p.Arg6Leu	missense_variant	Exon 1 of 12		NP_001268675.1
MLIP	NM_138569.3	c.17G>T	p.Arg6Leu	missense_variant	Exon 1 of 13		NP_612636.2
MLIP	XM_005249476.6	c.17G>T	p.Arg6Leu	missense_variant	Exon 1 of 14		XP_005249533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLIP	ENST00000514921.5	c.17G>T	p.Arg6Leu	missense_variant	Exon 1 of 12	1		ENSP00000425142.1
MLIP	ENST00000274897.9	c.17G>T	p.Arg6Leu	missense_variant	Exon 1 of 13	2		ENSP00000274897.5
MLIP	ENST00000370877.6	c.17G>T	p.Arg6Leu	missense_variant	Exon 1 of 8	5		ENSP00000359914.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458482 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725626

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0067	.;T;T;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.55	T;T;T;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.073	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N;N;.;.
PROVEAN	Benign	-0.44	N;N;N;N
REVEL	Benign	0.095
Sift	Benign	0.090	T;D;D;D
Sift4G	Benign	0.065	T;T;T;T
Polyphen		0.0010	.;B;.;.
Vest4		0.20
MutPred		0.24		Loss of MoRF binding (P = 0.0065);Loss of MoRF binding (P = 0.0065);Loss of MoRF binding (P = 0.0065);Loss of MoRF binding (P = 0.0065);
MVP		0.14
MPC		0.011
ClinPred		0.45	T
GERP RS		3.5
Varity_R		0.061

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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: chr6-53883843;