16-30116846-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001040056.3(MAPK3):​c.1065G>A​(p.Gly355Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000924 in 1,613,164 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0050 ( 7 hom., cov: 31)
Exomes 𝑓: 0.00050 ( 10 hom. )

Consequence

MAPK3
NM_001040056.3 synonymous

Scores

2

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0760
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 16-30116846-C-T is Benign according to our data. Variant chr16-30116846-C-T is described in ClinVar as [Benign]. Clinvar id is 3056883.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=0.076 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00497 (757/152224) while in subpopulation AFR AF= 0.0172 (714/41516). AF 95% confidence interval is 0.0162. There are 7 homozygotes in gnomad4. There are 377 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 757 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAPK3NM_002746.3 linkc.1017+48G>A intron_variant Intron 7 of 8 ENST00000263025.9 NP_002737.2 P27361-1L7RXH5
MAPK3NM_001040056.3 linkc.1065G>A p.Gly355Gly synonymous_variant Exon 7 of 7 NP_001035145.1 P27361-3
MAPK3NM_001109891.2 linkc.885+48G>A intron_variant Intron 6 of 7 NP_001103361.1 P27361-2Q9BWJ1
MAPK3XR_243293.2 linkn.1028+48G>A intron_variant Intron 7 of 9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAPK3ENST00000263025.9 linkc.1017+48G>A intron_variant Intron 7 of 8 1 NM_002746.3 ENSP00000263025.4 P27361-1

Frequencies

GnomAD3 genomes
AF:
0.00498
AC:
757
AN:
152106
Hom.:
7
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0172
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00229
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00131
AC:
322
AN:
246546
Hom.:
3
AF XY:
0.000864
AC XY:
116
AN XY:
134280
show subpopulations
Gnomad AFR exome
AF:
0.0182
Gnomad AMR exome
AF:
0.000957
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000272
Gnomad OTH exome
AF:
0.000331
GnomAD4 exome
AF:
0.000502
AC:
733
AN:
1460940
Hom.:
10
Cov.:
32
AF XY:
0.000422
AC XY:
307
AN XY:
726758
show subpopulations
Gnomad4 AFR exome
AF:
0.0188
Gnomad4 AMR exome
AF:
0.00101
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:
0.00000720
Gnomad4 OTH exome
AF:
0.000778
GnomAD4 genome
AF:
0.00497
AC:
757
AN:
152224
Hom.:
7
Cov.:
31
AF XY:
0.00506
AC XY:
377
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.0172
Gnomad4 AMR
AF:
0.00229
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00158
Hom.:
1
Bravo
AF:
0.00596
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

MAPK3-related disorder Benign:1
Oct 28, 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
-0.84
CADD
Benign
1.4
DANN
Benign
0.37

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: rs41291696; hg19: chr16-30128167; API