chr16-1706348-G-A

Variant names:

• chr16-1706348-G-A
• rs139282045
• NM_001318852.2:c.9G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001318852.2(MAPK8IP3):​c.9G>A​(p.Glu3Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00699 in 1,586,738 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0072 (60 hom.)
• Consequence: MAPK8IP3 NM_001318852.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 2.69
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 16-1706348-G-A is Benign according to our data. Variant chr16-1706348-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1675598.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.68 with no splicing effect.
• BS2: High AC in GnomAd4 at 731 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.9G>A	p.Glu3Glu	synonymous	Exon 1 of 32	NP_001305781.1	A0A087WYG2
	MAPK8IP3	NM_015133.5		c.9G>A	p.Glu3Glu	synonymous	Exon 1 of 32	NP_055948.2	Q9UPT6-1
	MAPK8IP3	NM_001040439.2		c.9G>A	p.Glu3Glu	synonymous	Exon 1 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.9G>A	p.Glu3Glu	synonymous	Exon 1 of 32	ENSP00000481780.1	A0A087WYG2
	MAPK8IP3	ENST00000250894.8	TSL:1	c.9G>A	p.Glu3Glu	synonymous	Exon 1 of 32	ENSP00000250894.4	Q9UPT6-1
	MAPK8IP3	ENST00000673691.1		c.9G>A	p.Glu3Glu	synonymous	Exon 1 of 33	ENSP00000501096.1	A0A669KB35

Frequencies

GnomAD3 genomes AF: 0.00481 AC: 732 AN: 152180 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00556

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00841

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00566 AC: 1163 AN: 205598 AF XY: 0.00545

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00263

Gnomad ASJ exome AF: 0.000109

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00637

Gnomad NFE exome AF: 0.0104

Gnomad OTH exome AF: 0.00541

GnomAD4 exome AF: 0.00723 AC: 10367 AN: 1434442 Hom.: 60 Cov.: 31 AF XY: 0.00697 AC XY: 4961 AN XY: 711324

African (AFR) AF: 0.00101 AC: 33 AN: 32714

American (AMR) AF: 0.00265 AC: 110 AN: 41490

Ashkenazi Jewish (ASJ) AF: 0.000313 AC: 8 AN: 25600

East Asian (EAS) AF: 0.00 AC: 0 AN: 38084

South Asian (SAS) AF: 0.000132 AC: 11 AN: 83422

European-Finnish (FIN) AF: 0.00756 AC: 367 AN: 48562

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5646

European-Non Finnish (NFE) AF: 0.00870 AC: 9564 AN: 1099650

Other (OTH) AF: 0.00461 AC: 273 AN: 59274

GnomAD4 genome AF: 0.00480 AC: 731 AN: 152296 Hom.: 1 Cov.: 32 AF XY: 0.00426 AC XY: 317 AN XY: 74474

African (AFR) AF: 0.00125 AC: 52 AN: 41578

American (AMR) AF: 0.00268 AC: 41 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00556 AC: 59 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00841 AC: 572 AN: 68010

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00479 Hom.: 0

Bravo AF: 0.00487

Asia WGS AF: 0.000578 AC: 2 AN: 3474

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	MAPK8IP3-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	13
DANN	Benign	0.87
PhyloP100		2.7
PromoterAI		-0.013	Neutral
Mutation Taster		=100/0	polymorphism

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: rs139282045; hg19: chr16-1756349;