6-16143730-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_013262.4(MYLIP):c.694C>A(p.Gln232Lys) 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 pathogenic 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.55

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.801

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYLIP	NM_013262.4	c.694C>A	p.Gln232Lys	missense_variant	5/7	ENST00000356840.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYLIP	ENST00000356840.8	c.694C>A	p.Gln232Lys	missense_variant	5/7	1	NM_013262.4	P1
MYLIP	ENST00000349606.4	c.151C>A	p.Gln51Lys	missense_variant	4/6	1

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2023

The c.694C>A (p.Q232K) alteration is located in exon 5 (coding exon 5) of the MYLIP gene. This alteration results from a C to A substitution at nucleotide position 694, causing the glutamine (Q) at amino acid position 232 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.36	T;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Uncertain	0.096	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Benign	1.7	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.98	N;N
REVEL	Uncertain	0.30
Sift	Benign	0.13	T;T
Sift4G	Benign	0.39	T;T
Polyphen		0.92	P;.
Vest4		0.82
MutPred		0.59		Gain of ubiquitination at Q232 (P = 0.0325);.;
MVP		0.90
MPC		0.36
ClinPred		0.65	D
GERP RS		5.5
Varity_R		0.65
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr6-16143961;