6-16143159-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_013262.4(MYLIP):c.604A>C(p.Ile202Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0177 in 1,614,190 control chromosomes in the GnomAD database, including 304 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (22 hom., cov: 32)
  • Exomes 𝑓: 0.018 (282 hom.)
• Consequence: MYLIP NM_013262.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.97

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010784149).
• BP6: Variant 6-16143159-A-C is Benign according to our data. Variant chr6-16143159-A-C is described in ClinVar as [Benign]. Clinvar id is 1599503.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-16143159-A-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0138 (2100/152308) while in subpopulation NFE AF= 0.0186 (1267/68026). AF 95% confidence interval is 0.0178. There are 22 homozygotes in gnomad4. There are 966 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 22 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYLIP	NM_013262.4	c.604A>C	p.Ile202Leu	missense_variant	4/7	ENST00000356840.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYLIP	ENST00000356840.8	c.604A>C	p.Ile202Leu	missense_variant	4/7	1	NM_013262.4	P1
MYLIP	ENST00000349606.4	c.61A>C	p.Ile21Leu	missense_variant	3/6	1

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2102 AN: 152190 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.00307

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0171

Gnomad ASJ AF: 0.0703

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0103

Gnomad FIN AF: 0.00847

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0186

Gnomad OTH AF: 0.0167

GnomAD3 exomes AF: 0.0154 AC: 3876 AN: 251484 Hom.: 47 AF XY: 0.0157 AC XY: 2130 AN XY: 135918

Gnomad AFR exome AF: 0.00240

Gnomad AMR exome AF: 0.00856

Gnomad ASJ exome AF: 0.0680

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0120

Gnomad FIN exome AF: 0.00975

Gnomad NFE exome AF: 0.0192

Gnomad OTH exome AF: 0.0145

GnomAD4 exome AF: 0.0181 AC: 26493 AN: 1461882 Hom.: 282 Cov.: 31 AF XY: 0.0181 AC XY: 13151 AN XY: 727242

Gnomad4 AFR exome AF: 0.00227

Gnomad4 AMR exome AF: 0.00923

Gnomad4 ASJ exome AF: 0.0688

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0115

Gnomad4 FIN exome AF: 0.0103

Gnomad4 NFE exome AF: 0.0193

Gnomad4 OTH exome AF: 0.0190

GnomAD4 genome AF: 0.0138 AC: 2100 AN: 152308 Hom.: 22 Cov.: 32 AF XY: 0.0130 AC XY: 966 AN XY: 74474

Gnomad4 AFR AF: 0.00306

Gnomad4 AMR AF: 0.0171

Gnomad4 ASJ AF: 0.0703

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0101

Gnomad4 FIN AF: 0.00847

Gnomad4 NFE AF: 0.0186

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0197 Hom.: 68

Bravo AF: 0.0141

TwinsUK AF: 0.0181 AC: 67

ALSPAC AF: 0.0189 AC: 73

ESP6500AA AF: 0.00431 AC: 19

ESP6500EA AF: 0.0199 AC: 171

ExAC AF: 0.0149 AC: 1807

Asia WGS AF: 0.00722 AC: 25 AN: 3478

EpiCase AF: 0.0205

EpiControl AF: 0.0219

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	19
Dann	Benign	0.97
DEOGEN2	Benign	0.34	T;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D;D
MetaRNN	Benign	0.011	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.26	N;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.056
Sift	Benign	0.080	T;T
Sift4G	Benign	0.39	T;T
Polyphen		0.0010	B;.
Vest4		0.59
MPC		0.17
ClinPred		0.026	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.39
gMVP		0.63

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

LitVar

Other links and lift over

dbSNP: rs79992066; hg19: chr6-16143390;