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GeneBe

6-16143097-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_013262.4(MYLIP):c.542C>T(p.Ala181Val) variant causes a missense change involving the alteration of a 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: 32)

Consequence

MYLIP
NM_013262.4 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.46
Variant links:
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]

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ACMG classification

Classification made for transcript

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=0.38287646).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MYLIPNM_013262.4 linkuse as main transcriptc.542C>T p.Ala181Val missense_variant 4/7 ENST00000356840.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MYLIPENST00000356840.8 linkuse as main transcriptc.542C>T p.Ala181Val missense_variant 4/71 NM_013262.4 P1Q8WY64-1
MYLIPENST00000349606.4 linkuse as main transcriptc.-2C>T 5_prime_UTR_variant 3/61

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeNov 18, 2023This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 181 of the MYLIP protein (p.Ala181Val). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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
Benign
0.095
BayesDel_addAF
Uncertain
0.014
T
BayesDel_noAF
Benign
-0.22
Cadd
Benign
22
Dann
Uncertain
0.99
DEOGEN2
Benign
0.21
T
Eigen
Benign
-0.12
Eigen_PC
Benign
-0.030
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.044
D
MetaRNN
Benign
0.38
T
MetaSVM
Benign
-0.73
T
MutationAssessor
Benign
1.2
L
MutationTaster
Benign
0.91
D;D
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.27
Sift
Benign
0.23
T
Sift4G
Benign
0.23
T
Polyphen
0.085
B
Vest4
0.43
MutPred
0.45
Gain of helix (P = 0.2059);
MVP
0.89
MPC
0.22
ClinPred
0.62
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.16
gMVP
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: chr6-16143328; API