3-40170082-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015460.4(MYRIP):​c.862G>T​(p.Ala288Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

MYRIP
NM_015460.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.19
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.038446873).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYRIPNM_015460.4 linkc.862G>T p.Ala288Ser missense_variant Exon 8 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.862G>T p.Ala288Ser missense_variant Exon 8 of 17 1 NM_015460.4 ENSP00000301972.6 Q8NFW9-1

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152216
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
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
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
251010
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135680
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461794
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
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:
0.0000497
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152216
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000869

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
0.0030
DANN
Benign
0.23
DEOGEN2
Benign
0.014
T;T;.;.;.
Eigen
Benign
-1.8
Eigen_PC
Benign
-2.0
FATHMM_MKL
Benign
0.0057
N
LIST_S2
Benign
0.53
.;T;T;T;T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.038
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N;N;.;N;.
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-0.43
N;N;N;N;N
REVEL
Benign
0.0080
Sift
Benign
0.73
T;T;T;T;T
Sift4G
Benign
0.78
T;T;T;T;T
Polyphen
0.0010
B;B;.;.;.
Vest4
0.12
MutPred
0.19
Gain of glycosylation at Y284 (P = 0.0039);Gain of glycosylation at Y284 (P = 0.0039);.;Gain of glycosylation at Y284 (P = 0.0039);.;
MVP
0.099
MPC
0.095
ClinPred
0.042
T
GERP RS
-9.1
Varity_R
0.024
gMVP
0.069

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: rs376404162; hg19: chr3-40211573; API