16-30121850-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002746.3(MAPK3):c.327G>A(p.Ala109=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000623 in 1,613,928 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 0.00041 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00065 (1 hom.)
• Consequence: MAPK3 NM_002746.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.15

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 16-30121850-C-T is Benign according to our data. Variant chr16-30121850-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 726200.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.15 with no splicing effect.
• BS2: High AC in GnomAd at 63 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPK3	NM_002746.3	c.327G>A	p.Ala109=	synonymous_variant	2/9	ENST00000263025.9
MAPK3	NM_001040056.3	c.327G>A	p.Ala109=	synonymous_variant	2/7
MAPK3	NM_001109891.2	c.327G>A	p.Ala109=	synonymous_variant	2/8
MAPK3	XR_243293.2	n.338G>A		non_coding_transcript_exon_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPK3	ENST00000263025.9	c.327G>A	p.Ala109=	synonymous_variant	2/9	1	NM_002746.3	P1

Frequencies

GnomAD3 genomes AF: 0.000414 AC: 63 AN: 152198 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000705

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000419 AC: 105 AN: 250884 Hom.: 0 AF XY: 0.000383 AC XY: 52 AN XY: 135664

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.000325

Gnomad NFE exome AF: 0.000758

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000645 AC: 943 AN: 1461730 Hom.: 1 Cov.: 31 AF XY: 0.000639 AC XY: 465 AN XY: 727168

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.0000671

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.000356

Gnomad4 NFE exome AF: 0.000801

Gnomad4 OTH exome AF: 0.000265

GnomAD4 genome AF: 0.000414 AC: 63 AN: 152198 Hom.: 0 Cov.: 31 AF XY: 0.000390 AC XY: 29 AN XY: 74348

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.000705

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.000459 Hom.: 0

Bravo AF: 0.000404

EpiCase AF: 0.000654

EpiControl AF: 0.000474

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

Jul 06, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	6.0
Dann	Benign	0.89

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: rs151100121; hg19: chr16-30133171; COSMIC: COSV53777718; COSMIC: COSV53777718;