16-1724639-G-C

Variant names:

• chr16-1724639-G-C
• rs376978493
• NM_001318852.2:c.401G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001318852.2(MAPK8IP3):​c.401G>C​(p.Arg134Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,184 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MAPK8IP3 NM_001318852.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.06

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK8IP3	NM_001318852.2	c.401G>C	p.Arg134Pro	missense_variant	Exon 2 of 32	ENST00000610761.2	NP_001305781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK8IP3	ENST00000610761.2	c.401G>C	p.Arg134Pro	missense_variant	Exon 2 of 32	1	NM_001318852.2	ENSP00000481780.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461184 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726878

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000119 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D;T;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.67	D;D;D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Uncertain	2.7	M;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.1	D;D;.
REVEL	Uncertain	0.37
Sift	Uncertain	0.0010	D;D;.
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		0.99	D;D;.
Vest4		0.59
MVP		0.56
MPC		1.6
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.89
gMVP		0.95

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

Publications

LitVar

Other links and lift over

dbSNP: rs376978493; hg19: chr16-1774640;