Menu
GeneBe

16-30118415-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002746.3(MAPK3):c.477C>T(p.Ser159=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 1,599,700 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

MAPK3
NM_002746.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.89
Variant links:
Genes affected
MAPK3 (HGNC:6877): (mitogen-activated protein kinase 3) The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 16-30118415-G-A is Benign according to our data. Variant chr16-30118415-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3047898.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-4.89 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 38 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MAPK3NM_002746.3 linkuse as main transcriptc.477C>T p.Ser159= synonymous_variant 3/9 ENST00000263025.9
MAPK3NM_001040056.3 linkuse as main transcriptc.477C>T p.Ser159= synonymous_variant 3/7
MAPK3NM_001109891.2 linkuse as main transcriptc.477C>T p.Ser159= synonymous_variant 3/8
MAPK3XR_243293.2 linkuse as main transcriptn.488C>T non_coding_transcript_exon_variant 3/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MAPK3ENST00000263025.9 linkuse as main transcriptc.477C>T p.Ser159= synonymous_variant 3/91 NM_002746.3 P1P27361-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000276
AC:
38
AN:
137916
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000274
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000639
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00236
Gnomad SAS
AF:
0.000241
Gnomad FIN
AF:
0.0000992
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000225
Gnomad OTH
AF:
0.000539
GnomAD3 exomes
AF:
0.000267
AC:
67
AN:
251142
Hom.:
0
AF XY:
0.000221
AC XY:
30
AN XY:
135718
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000376
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00174
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000123
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000185
AC:
270
AN:
1461662
Hom.:
1
Cov.:
32
AF XY:
0.000186
AC XY:
135
AN XY:
727136
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.000336
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000706
Gnomad4 SAS exome
AF:
0.000174
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000176
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000275
AC:
38
AN:
138038
Hom.:
0
Cov.:
31
AF XY:
0.000384
AC XY:
26
AN XY:
67690
show subpopulations
Gnomad4 AFR
AF:
0.0000273
Gnomad4 AMR
AF:
0.000638
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00237
Gnomad4 SAS
AF:
0.000241
Gnomad4 FIN
AF:
0.0000992
Gnomad4 NFE
AF:
0.000225
Gnomad4 OTH
AF:
0.000533
Alfa
AF:
0.000176
Hom.:
0
Bravo
AF:
0.000276
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

MAPK3-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesFeb 22, 2019This variant is classified as likely 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
-0.71
Cadd
Benign
0.41
Dann
Benign
0.80

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs142560490; hg19: chr16-30129736; COSMIC: COSV53772892; COSMIC: COSV53772892; API