chr16-1706387-G-C

Variant names:

• chr16-1706387-G-C
• rs2037387594
• NM_001318852.2:c.48G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001318852.2(MAPK8IP3):​c.48G>C​(p.Gln16His) variant causes a missense change. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q16R) has been classified 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: 4.39
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22272894).

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.48G>C	p.Gln16His	missense	Exon 1 of 32	NP_001305781.1	A0A087WYG2
	MAPK8IP3	NM_015133.5		c.48G>C	p.Gln16His	missense	Exon 1 of 32	NP_055948.2	Q9UPT6-1
	MAPK8IP3	NM_001040439.2		c.48G>C	p.Gln16His	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.48G>C	p.Gln16His	missense	Exon 1 of 32	ENSP00000481780.1	A0A087WYG2
	MAPK8IP3	ENST00000250894.8	TSL:1	c.48G>C	p.Gln16His	missense	Exon 1 of 32	ENSP00000250894.4	Q9UPT6-1
	MAPK8IP3	ENST00000561765.1	TSL:1	n.9G>C		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000629 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.044
Eigen_PC	Benign	0.0062
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.4
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.069
Sift	Uncertain	0.014	D
Sift4G	Benign	0.13	T
Polyphen		0.88	P
Vest4		0.17
MutPred		0.24		Loss of stability (P = 0.1625)
MVP		0.49
MPC		0.95
ClinPred		0.69	D
GERP RS		2.3
PromoterAI		-0.061	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.18
gMVP		0.68
Mutation Taster		=73/27	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: rs2037387594; hg19: chr16-1756388;