16-30123177-G-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_002746.3(MAPK3):c.33C>G(p.Gly11=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (0 hom., cov: 13)
  • Exomes 𝑓: 0.0030 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAPK3 NM_002746.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.32

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 16-30123177-G-C is Benign according to our data. Variant chr16-30123177-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 774921.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.32 with no splicing effect.
• BS2: High AC in GnomAdExome at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK3	NM_002746.3	c.33C>G	p.Gly11=	synonymous_variant	1/9	ENST00000263025.9
MAPK3	NM_001040056.3	c.33C>G	p.Gly11=	synonymous_variant	1/7
MAPK3	NM_001109891.2	c.33C>G	p.Gly11=	synonymous_variant	1/8
MAPK3	XR_243293.2	n.44C>G		non_coding_transcript_exon_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK3	ENST00000263025.9	c.33C>G	p.Gly11=	synonymous_variant	1/9	1	NM_002746.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1058 AN: 55060 Hom.: 0 Cov.: 13 FAILED QC

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.00350

Gnomad AMR AF: 0.0142

Gnomad ASJ AF: 0.0214

Gnomad EAS AF: 0.00668

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0199

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0226

Gnomad OTH AF: 0.0233

GnomAD3 exomes AF: 0.000216 AC: 11 AN: 50844 Hom.: 0 AF XY: 0.000278 AC XY: 8 AN XY: 28792

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00112

Gnomad NFE exome AF: 0.0000546

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00303 AC: 1694 AN: 559854 Hom.: 0 Cov.: 14 AF XY: 0.00307 AC XY: 861 AN XY: 280830

Gnomad4 AFR exome AF: 0.00183

Gnomad4 AMR exome AF: 0.00175

Gnomad4 ASJ exome AF: 0.00207

Gnomad4 EAS exome AF: 0.00354

Gnomad4 SAS exome AF: 0.00414

Gnomad4 FIN exome AF: 0.00562

Gnomad4 NFE exome AF: 0.00282

Gnomad4 OTH exome AF: 0.00405

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0192 AC: 1059 AN: 55114 Hom.: 0 Cov.: 13 AF XY: 0.0192 AC XY: 532 AN XY: 27690

Gnomad4 AFR AF: 0.0185

Gnomad4 AMR AF: 0.0141

Gnomad4 ASJ AF: 0.0214

Gnomad4 EAS AF: 0.00671

Gnomad4 SAS AF: 0.0106

Gnomad4 FIN AF: 0.0199

Gnomad4 NFE AF: 0.0226

Gnomad4 OTH AF: 0.0232

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	15
Dann	Benign	0.44

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: rs1368575816; hg19: chr16-30134498;