ENST00000514921.5:c.40A>G

Variant names:

• chr6-54019068-A-G
• ENST00000514921.5:c.40A>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000514921.5(MLIP):​c.40A>G​(p.Lys14Glu) variant causes a missense 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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MLIP ENST00000514921.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.164

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029019177).
• BP6: Variant 6-54019068-A-G is Benign according to our data. Variant chr6-54019068-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2246985.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLIP	NM_001281746.2	c.40A>G	p.Lys14Glu	missense_variant	Exon 1 of 12		NP_001268675.1
MLIP	NM_138569.3	c.40A>G	p.Lys14Glu	missense_variant	Exon 1 of 13		NP_612636.2
MLIP	XM_005249476.6	c.40A>G	p.Lys14Glu	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.40A>G	p.Lys14Glu	missense_variant	Exon 1 of 12	1		ENSP00000425142.1
MLIP	ENST00000274897.9	c.40A>G	p.Lys14Glu	missense_variant	Exon 1 of 13	2		ENSP00000274897.5
MLIP	ENST00000370877.6	c.40A>G	p.Lys14Glu	missense_variant	Exon 1 of 8	5		ENSP00000359914.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Benign:1

Aug 28, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.9
DANN	Benign	0.89
DEOGEN2	Benign	0.0021	.;T;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.56	T;T;T;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.029	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.0	L;L;.;.
PROVEAN	Benign	-0.11	N;N;N;N
REVEL	Benign	0.045
Sift	Benign	0.50	T;T;T;T
Sift4G	Benign	0.32	T;T;T;T
Polyphen		0.0	.;B;.;.
Vest4		0.10
MutPred		0.15		Loss of ubiquitination at K14 (P = 0.0056);Loss of ubiquitination at K14 (P = 0.0056);Loss of ubiquitination at K14 (P = 0.0056);Loss of ubiquitination at K14 (P = 0.0056);
MVP		0.014
MPC		0.011
ClinPred		0.029	T
GERP RS		-3.8
Varity_R		0.088

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-53883866;