dbSNP rs35459652: MAPK8IP3:p.Tyr129Tyr (chr16-1724625-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with or without variable brain abnormalities; NEDBA
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics

MAPK8IP3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2847 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318852.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAPK8IP3	NM_001318852.2	MANE Select	c.387C>T	p.Tyr129Tyr	synonymous	Exon 2 of 32	NP_001305781.1	A0A087WYG2
MAPK8IP3	NM_015133.5		c.387C>T	p.Tyr129Tyr	synonymous	Exon 2 of 32	NP_055948.2	Q9UPT6-1
MAPK8IP3	NM_001040439.2		c.387C>T	p.Tyr129Tyr	synonymous	Exon 2 of 31	NP_001035529.1	E9PFH7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAPK8IP3	ENST00000610761.2	TSL:1 MANE Select	c.387C>T	p.Tyr129Tyr	synonymous	Exon 2 of 32	ENSP00000481780.1	A0A087WYG2
MAPK8IP3	ENST00000250894.8	TSL:1	c.387C>T	p.Tyr129Tyr	synonymous	Exon 2 of 32	ENSP00000250894.4	Q9UPT6-1
MAPK8IP3	ENST00000561765.1	TSL:1	n.348C>T		non_coding_transcript_exon	Exon 2 of 6

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

GnomAD2 exomes

AF:

0.0190

AC:

4719

AN:

248984

AF XY:

0.0190

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 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

African (AFR)

AF:

0.00427

AC:

143

AN:

33480

American (AMR)

AF:

0.0136

AC:

609

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0162

AC:

424

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00311

AC:

268

AN:

86256

European-Finnish (FIN)

AF:

0.0325

AC:

1720

AN:

52894

Middle Eastern (MID)

AF:

0.0116

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0263

AC:

29218

AN:

1111894

Other (OTH)

AF:

0.0197

AC:

1188

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

1686

3371

5057

6742

8428

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1044

2088

3132

4176

5220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0187

AC:

2847

AN:

152356

Hom.:

Cov.:

AF XY:

0.0189

AC XY:

1408

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.00488

AC:

203

AN:

41594

American (AMR)

AF:

0.0215

AC:

329

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0147

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00393

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0314

AC:

333

AN:

10616

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0268

AC:

1822

AN:

68038

Other (OTH)

AF:

0.0232

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

146

292

438

584

730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0193

Hom.:

Bravo

AF:

0.0172

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

MAPK8IP3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.31

(source)

DANN

Benign

0.29

PhyloP100

-0.26

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over