16-1724625-C-T

Variant names:

• chr16-1724625-C-T
• rs35459652
• NM_001318852.2:c.387C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.256
• Publications: 4 publications found

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

ACMG classification

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

Sel.	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

Sel.	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.: 40 Cov.: 32

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

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.: 31 AF XY: 0.0227 AC XY: 16469 AN XY: 726904

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: 1 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: 67 AN: 5764

European-Non Finnish (NFE) AF: 0.0263 AC: 29218 AN: 1111894

Other (OTH) AF: 0.0197 AC: 1188 AN: 60378

GnomAD4 genome AF: 0.0187 AC: 2847 AN: 152356 Hom.: 40 Cov.: 32 AF XY: 0.0189 AC XY: 1408 AN XY: 74506

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: 51 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00393 AC: 19 AN: 4832

European-Finnish (FIN) AF: 0.0314 AC: 333 AN: 10616

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0268 AC: 1822 AN: 68038

Other (OTH) AF: 0.0232 AC: 49 AN: 2116

Alfa AF: 0.0193 Hom.: 26

Bravo AF: 0.0172

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MAPK8IP3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.31
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)

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

Other links and lift over

dbSNP: rs35459652; hg19: chr16-1774626;