chr6-16141730-T-G

Position:

• chr6-16141730-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_013262.4(MYLIP):​c.384T>G​(p.Phe128Leu) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYLIP NM_013262.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.202

Genes affected

MYLIP (HGNC:21155): (myosin regulatory light chain interacting protein) The ERM protein family members ezrin, radixin, and moesin are cytoskeletal effector proteins linking actin to membrane-bound proteins at the cell surface. Myosin regulatory light chain interacting protein (MYLIP) is a novel ERM-like protein that interacts with myosin regulatory light chain and inhibits neurite outgrowth. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34905946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYLIP	NM_013262.4	c.384T>G	p.Phe128Leu	missense_variant	3/7	ENST00000356840.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYLIP	ENST00000356840.8	c.384T>G	p.Phe128Leu	missense_variant	3/7	1	NM_013262.4	P1
MYLIP	ENST00000349606.4	c.-160T>G		5_prime_UTR_variant	2/6	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2023

Does not currently meet published gene-disease clinical validity criteria Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Feb 11, 2023

This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 128 of the MYLIP protein (p.Phe128Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MYLIP-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	16
DANN	Benign	0.87
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.54
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.26	N
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.19
Sift	Benign	0.43	T
Sift4G	Benign	0.68	T
Polyphen		0.15	B
Vest4		0.58
MutPred		0.66		Loss of methylation at K127 (P = 0.0991);
MVP		0.47
MPC		0.21
ClinPred		0.34	T
GERP RS		-1.7
Varity_R		0.36
gMVP		0.59

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: chr6-16141961;