chr16-1706401-C-A

Variant names:

• chr16-1706401-C-A
• NM_001318852.2:c.62C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001318852.2(MAPK8IP3):​c.62C>A​(p.Ser21Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAPK8IP3 NM_001318852.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.51
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35949498).

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.62C>A	p.Ser21Tyr	missense	Exon 1 of 32	NP_001305781.1	A0A087WYG2
	MAPK8IP3	NM_015133.5		c.62C>A	p.Ser21Tyr	missense	Exon 1 of 32	NP_055948.2	Q9UPT6-1
	MAPK8IP3	NM_001040439.2		c.62C>A	p.Ser21Tyr	missense	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.62C>A	p.Ser21Tyr	missense	Exon 1 of 32	ENSP00000481780.1	A0A087WYG2
	MAPK8IP3	ENST00000250894.8	TSL:1	c.62C>A	p.Ser21Tyr	missense	Exon 1 of 32	ENSP00000250894.4	Q9UPT6-1
	MAPK8IP3	ENST00000561765.1	TSL:1	n.23C>A		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Pathogenic	0.55	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.5
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.010	D
Polyphen		0.84	P
Vest4		0.32
MutPred		0.33		Gain of catalytic residue at S21 (P = 0.007)
MVP		0.43
MPC		1.4
ClinPred		0.96	D
GERP RS		3.3
PromoterAI		-0.048	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.51
gMVP		0.64
Mutation Taster		=61/39	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

hg19: chr16-1756402;