Variant NM_001318852.2:c.387C>T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001318852.2(MAPK8IP3):c.387C>T(p.Tyr129Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 1,613,574 control chromosomes in the GnomAD database, including 502 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.019 ( 40 hom., cov: 32)

Exomes 𝑓: 0.023 ( 462 hom. )

Consequence

MAPK8IP3
NM_001318852.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.256

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]

MAPK8IP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 16-1724625-C-T is Benign according to our data. Variant chr16-1724625-C-T is described in ClinVar as [Benign]. Clinvar id is 3056907.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.256 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0187 (2847/152356) while in subpopulation NFE AF= 0.0268 (1822/68038). AF 95% confidence interval is 0.0258. There are 40 homozygotes in gnomad4. There are 1408 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2847 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK8IP3	NM_001318852.2 link	c.387C>T	p.Tyr129Tyr	synonymous_variant	Exon 2 of 32	ENST00000610761.2	NP_001305781.1	Q9UPT6A0A087WYG2B7ZMF3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK8IP3	ENST00000610761.2 link	c.387C>T	p.Tyr129Tyr	synonymous_variant	Exon 2 of 32	1	NM_001318852.2	ENSP00000481780.1		A0A087WYG2

Frequencies

GnomAD3 genomes

AF:

0.0187

AC:

2846

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00489

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0215

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.0314

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0268

Gnomad OTH

AF:

0.0234

GnomAD3 exomes

AF:

0.0190

AC:

4719

AN:

248984

Hom.:

AF XY:

0.0190

AC XY:

2565

AN XY:

135270

show subpopulations

Gnomad AFR exome

AF:

0.00382

Gnomad AMR exome

AF:

0.0123

Gnomad ASJ exome

AF:

0.0166

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00297

Gnomad FIN exome

AF:

0.0302

Gnomad NFE exome

AF:

0.0284

Gnomad OTH exome

AF:

0.0203

GnomAD4 exome

AF:

0.0230

AC:

33638

AN:

1461218

Hom.:

462

Cov.:

AF XY:

0.0227

AC XY:

16469

AN XY:

726904

show subpopulations

Gnomad4 AFR exome

AF:

0.00427

Gnomad4 AMR exome

AF:

0.0136

Gnomad4 ASJ exome

AF:

0.0162

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00311

Gnomad4 FIN exome

AF:

0.0325

Gnomad4 NFE exome

AF:

0.0263

Gnomad4 OTH exome

AF:

0.0197

GnomAD4 genome

AF:

0.0187

AC:

2847

AN:

152356

Hom.:

Cov.:

AF XY:

0.0189

AC XY:

1408

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00488

Gnomad4 AMR

AF:

0.0215

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00393

Gnomad4 FIN

AF:

0.0314

Gnomad4 NFE

AF:

0.0268

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.0221

Hom.:

Bravo

AF:

0.0172

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MAPK8IP3-related disorder

Benign:1

Nov 01, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This 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

-0.77

CADD

Benign

0.31

DANN

Benign

0.29

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over