Genetic Variant MYRIP:p.Asn123Ser (chr3-40151083-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015460.4(MYRIP):c.368A>G(p.Asn123Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MYRIP
NM_015460.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.76

Publications

0 publications found

Variant links:

Genes affected

MYRIP (HGNC:19156): (myosin VIIA and Rab interacting protein) Predicted to enable actin binding activity and myosin binding activity. Predicted to be involved in positive regulation of insulin secretion. Predicted to be located in actin cytoskeleton; dense core granule; and perinuclear region of cytoplasm. Predicted to be part of exocyst. Predicted to be active in cortical actin cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

MYRIP links:

EIF1B-AS1 (HGNC:):

EIF1B-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26001292).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYRIP	NM_015460.4 link	c.368A>G	p.Asn123Ser	missense_variant	Exon 4 of 17	ENST00000302541.11	NP_056275.2	Q8NFW9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYRIP	ENST00000302541.11 link	c.368A>G	p.Asn123Ser	missense_variant	Exon 4 of 17	1	NM_015460.4	ENSP00000301972.6		Q8NFW9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1456758

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724370

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33408

American (AMR)

AF:

0.00

AC:

AN:

44184

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26012

East Asian (EAS)

AF:

0.00

AC:

AN:

39518

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85206

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109312

Other (OTH)

AF:

0.0000166

AC:

AN:

60162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 18, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.368A>G (p.N123S) alteration is located in exon 4 (coding exon 3) of the MYRIP gene. This alteration results from a A to G substitution at nucleotide position 368, causing the asparagine (N) at amino acid position 123 to be replaced by a serine (S). 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

Benign

0.051

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

T;T;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.72

.;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.34

N;N;N

PhyloP100

2.8

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.3

N;N;N

REVEL

Benign

0.25

Sift

Benign

0.24

T;T;T

Sift4G

Benign

0.12

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.29

MutPred

0.42

Gain of glycosylation at Y122 (P = 0.0553);Gain of glycosylation at Y122 (P = 0.0553);Gain of glycosylation at Y122 (P = 0.0553);

MVP

0.76

MPC

0.083

ClinPred

0.77

GERP RS

3.6

Varity_R

0.14

gMVP

0.068

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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3-40151083-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over