16-1706378-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The ENST00000610761.2(MAPK8IP3):​c.39G>A​(p.Val13=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00676 in 1,610,328 control chromosomes in the GnomAD database, including 329 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0043 ( 14 hom., cov: 32)
Exomes 𝑓: 0.0070 ( 315 hom. )

Consequence

MAPK8IP3
ENST00000610761.2 synonymous

Scores

2

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.49
Variant links:
Genes affected
MAPK8IP3 (HGNC:6884): (mitogen-activated protein kinase 8 interacting protein 3) The protein encoded by this gene shares similarity with the product of Drosophila syd gene, required for the functional interaction of kinesin I with axonal cargo. Studies of the similar gene in mouse suggested that this protein may interact with, and regulate the activity of numerous protein kinases of the JNK signaling pathway, and thus function as a scaffold protein in neuronal cells. The C. elegans counterpart of this gene is found to regulate synaptic vesicle transport possibly by integrating JNK signaling and kinesin-1 transport. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
Variant 16-1706378-G-A is Benign according to our data. Variant chr16-1706378-G-A is described in ClinVar as [Benign]. Clinvar id is 3039422.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=1.49 with no splicing effect.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0726 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MAPK8IP3NM_001318852.2 linkuse as main transcriptc.39G>A p.Val13= synonymous_variant 1/32 ENST00000610761.2 NP_001305781.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAPK8IP3ENST00000610761.2 linkuse as main transcriptc.39G>A p.Val13= synonymous_variant 1/321 NM_001318852.2 ENSP00000481780 P4

Frequencies

GnomAD3 genomes
AF:
0.00430
AC:
654
AN:
152194
Hom.:
14
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00294
Gnomad ASJ
AF:
0.00547
Gnomad EAS
AF:
0.000578
Gnomad SAS
AF:
0.0786
Gnomad FIN
AF:
0.000283
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00231
Gnomad OTH
AF:
0.00335
GnomAD3 exomes
AF:
0.0116
AC:
2800
AN:
240906
Hom.:
108
AF XY:
0.0153
AC XY:
2006
AN XY:
131384
show subpopulations
Gnomad AFR exome
AF:
0.00107
Gnomad AMR exome
AF:
0.00171
Gnomad ASJ exome
AF:
0.00467
Gnomad EAS exome
AF:
0.00119
Gnomad SAS exome
AF:
0.0813
Gnomad FIN exome
AF:
0.000148
Gnomad NFE exome
AF:
0.00175
Gnomad OTH exome
AF:
0.00632
GnomAD4 exome
AF:
0.00701
AC:
10226
AN:
1458016
Hom.:
315
Cov.:
31
AF XY:
0.00926
AC XY:
6715
AN XY:
725102
show subpopulations
Gnomad4 AFR exome
AF:
0.000510
Gnomad4 AMR exome
AF:
0.00182
Gnomad4 ASJ exome
AF:
0.00392
Gnomad4 EAS exome
AF:
0.000633
Gnomad4 SAS exome
AF:
0.0791
Gnomad4 FIN exome
AF:
0.0000956
Gnomad4 NFE exome
AF:
0.00250
Gnomad4 OTH exome
AF:
0.00719
GnomAD4 genome
AF:
0.00431
AC:
657
AN:
152312
Hom.:
14
Cov.:
32
AF XY:
0.00567
AC XY:
422
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.000962
Gnomad4 AMR
AF:
0.00294
Gnomad4 ASJ
AF:
0.00547
Gnomad4 EAS
AF:
0.000579
Gnomad4 SAS
AF:
0.0791
Gnomad4 FIN
AF:
0.000283
Gnomad4 NFE
AF:
0.00231
Gnomad4 OTH
AF:
0.00379
Alfa
AF:
0.00226
Hom.:
2
Bravo
AF:
0.00204
Asia WGS
AF:
0.0440
AC:
152
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

MAPK8IP3-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesDec 02, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
CADD
Benign
12
DANN
Benign
0.90
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

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

Other links and lift over

dbSNP: rs201073807; hg19: chr16-1756379; API