3-40182279-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015460.4(MYRIP):​c.933G>T​(p.Glu311Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,122 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

MYRIP
NM_015460.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.46
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]
EIF1B-AS1 (HGNC:44555): (EIF1B antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.15835014).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYRIPNM_015460.4 linkc.933G>T p.Glu311Asp missense_variant Exon 9 of 17 ENST00000302541.11 NP_056275.2 Q8NFW9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYRIPENST00000302541.11 linkc.933G>T p.Glu311Asp missense_variant Exon 9 of 17 1 NM_015460.4 ENSP00000301972.6 Q8NFW9-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152122
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000194
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152122
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74302
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.933G>T (p.E311D) alteration is located in exon 9 (coding exon 8) of the MYRIP gene. This alteration results from a G to T substitution at nucleotide position 933, causing the glutamic acid (E) at amino acid position 311 to be replaced by an aspartic acid (D). 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
0.085
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
14
DANN
Uncertain
1.0
DEOGEN2
Benign
0.013
T;T;.;.;.
Eigen
Benign
0.080
Eigen_PC
Benign
-0.064
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.62
.;T;T;T;T
M_CAP
Benign
0.0093
T
MetaRNN
Benign
0.16
T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Uncertain
2.6
M;M;.;M;.
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.070
N;N;N;N;N
REVEL
Benign
0.15
Sift
Benign
0.075
T;T;T;T;T
Sift4G
Benign
0.58
T;T;T;T;T
Polyphen
1.0
D;D;.;.;.
Vest4
0.061
MutPred
0.11
Gain of glycosylation at T307 (P = 0.0291);Gain of glycosylation at T307 (P = 0.0291);.;Gain of glycosylation at T307 (P = 0.0291);.;
MVP
0.61
MPC
0.14
ClinPred
0.33
T
GERP RS
3.4
Varity_R
0.044
gMVP
0.045

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1259914372; hg19: chr3-40223770; API