6-16129378-C-A

Variant names:

• chr6-16129378-C-A
• NM_013262.4:c.56C>A

Variant summary

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

The NM_013262.4(MYLIP):​c.56C>A​(p.Ala19Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYLIP NM_013262.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.96

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24277699).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYLIP	NM_013262.4	c.56C>A	p.Ala19Glu	missense_variant	Exon 1 of 7	ENST00000356840.8	NP_037394.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYLIP	ENST00000356840.8	c.56C>A	p.Ala19Glu	missense_variant	Exon 1 of 7	1	NM_013262.4	ENSP00000349298.3
MYLIP	ENST00000349606	c.-297C>A		5_prime_UTR_variant	Exon 1 of 6	1		ENSP00000008686.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1441978 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 715586

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.56C>A (p.A19E) alteration is located in exon 1 (coding exon 1) of the MYLIP gene. This alteration results from a C to A substitution at nucleotide position 56, causing the alanine (A) at amino acid position 19 to be replaced by a glutamic acid (E). 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	Uncertain	0.35
BayesDel_addAF	Benign	0.0085	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.091
Eigen_PC	Benign	0.094
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.34	N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.17	N
REVEL	Benign	0.21
Sift	Benign	0.22	T
Sift4G	Benign	0.51	T
Polyphen		0.0080	B
Vest4		0.32
MutPred		0.49		Gain of disorder (P = 0.0169);
MVP		0.87
MPC		0.21
ClinPred		0.58	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.40
gMVP		0.74

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: chr6-16129609;