chr16-1706378-G-A

Variant names:

• chr16-1706378-G-A
• rs201073807
• NM_001318852.2:c.39G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001318852.2(MAPK8IP3):​c.39G>A​(p.Val13Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00676 in 1,610,328 control chromosomes in the GnomAD database, including 329 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0043 (14 hom., cov: 32)
  • Exomes 𝑓: 0.0070 (315 hom.)
• Consequence: MAPK8IP3 NM_001318852.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.49

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 16-1706378-G-A is Benign according to our data. Variant chr16-1706378-G-A is described in ClinVar as [Benign]. Clinvar id is 3039422.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.49 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPK8IP3	NM_001318852.2	c.39G>A	p.Val13Val	synonymous_variant	Exon 1 of 32	ENST00000610761.2	NP_001305781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPK8IP3	ENST00000610761.2	c.39G>A	p.Val13Val	synonymous_variant	Exon 1 of 32	1	NM_001318852.2	ENSP00000481780.1

Frequencies

GnomAD3 genomes AF: 0.00430 AC: 654 AN: 152194 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00294

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0786

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00231

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.0116 AC: 2800 AN: 240906 Hom.: 108 AF XY: 0.0153 AC XY: 2006 AN XY: 131384

Gnomad AFR exome AF: 0.00107

Gnomad AMR exome AF: 0.00171

Gnomad ASJ exome AF: 0.00467

Gnomad EAS exome AF: 0.00119

Gnomad SAS exome AF: 0.0813

Gnomad FIN exome AF: 0.000148

Gnomad NFE exome AF: 0.00175

Gnomad OTH exome AF: 0.00632

GnomAD4 exome AF: 0.00701 AC: 10226 AN: 1458016 Hom.: 315 Cov.: 31 AF XY: 0.00926 AC XY: 6715 AN XY: 725102

Gnomad4 AFR exome AF: 0.000510

Gnomad4 AMR exome AF: 0.00182

Gnomad4 ASJ exome AF: 0.00392

Gnomad4 EAS exome AF: 0.000633

Gnomad4 SAS exome AF: 0.0791

Gnomad4 FIN exome AF: 0.0000956

Gnomad4 NFE exome AF: 0.00250

Gnomad4 OTH exome AF: 0.00719

GnomAD4 genome AF: 0.00431 AC: 657 AN: 152312 Hom.: 14 Cov.: 32 AF XY: 0.00567 AC XY: 422 AN XY: 74486

Gnomad4 AFR AF: 0.000962

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00547

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0791

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00231

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00226 Hom.: 2

Bravo AF: 0.00204

Asia WGS AF: 0.0440 AC: 152 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MAPK8IP3-related disorder Benign:1

Dec 02, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs201073807; hg19: chr16-1756379;