16-1765963-CC-AT

Variant names:

• chr16-1765963-CC-AT
• NM_001318852.2:c.2450_2451delCCinsAT
• MAPK8IP3 p.Ala817Asp

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001318852.2(MAPK8IP3):​c.2450_2451delCCinsAT​(p.Ala817Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: MAPK8IP3 NM_001318852.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.27
• 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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.2450_2451delCCinsAT	p.Ala817Asp	missense	N/A	NP_001305781.1	A0A087WYG2
	MAPK8IP3	NM_015133.5		c.2447_2448delCCinsAT	p.Ala816Asp	missense	N/A	NP_055948.2	Q9UPT6-1
	MAPK8IP3	NM_001040439.2		c.2429_2430delCCinsAT	p.Ala810Asp	missense	N/A	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.2450_2451delCCinsAT	p.Ala817Asp	missense	N/A	ENSP00000481780.1	A0A087WYG2
	MAPK8IP3	ENST00000250894.8	TSL:1	c.2447_2448delCCinsAT	p.Ala816Asp	missense	N/A	ENSP00000250894.4	Q9UPT6-1
	MAPK8IP3	ENST00000673691.1		c.2471_2472delCCinsAT	p.Ala824Asp	missense	N/A	ENSP00000501096.1	A0A669KB35

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-1815964;