16-30116903-C-T

Variant names:

• chr16-30116903-C-T
• rs1143695
• NM_002746.3:c.1008G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002746.3(MAPK3):​c.1008G>A​(p.Pro336Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00274 in 1,613,914 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0027 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0027 (12 hom.)
• Consequence: MAPK3 NM_002746.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.480
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 16-30116903-C-T is Benign according to our data. Variant chr16-30116903-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 710826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.48 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00274 (3998/1461706) while in subpopulation MID AF = 0.0218 (126/5768). AF 95% confidence interval is 0.0187. There are 12 homozygotes in GnomAdExome4. There are 1993 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 418 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002746.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK3	NM_002746.3	MANE Select	c.1008G>A	p.Pro336Pro	synonymous	Exon 7 of 9	NP_002737.2	L7RXH5
	MAPK3	NM_001040056.3		c.1008G>A	p.Pro336Pro	synonymous	Exon 7 of 7	NP_001035145.1	P27361-3
	MAPK3	NM_001109891.2		c.876G>A	p.Pro292Pro	synonymous	Exon 6 of 8	NP_001103361.1	P27361-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK3	ENST00000263025.9	TSL:1 MANE Select	c.1008G>A	p.Pro336Pro	synonymous	Exon 7 of 9	ENSP00000263025.4	P27361-1
	MAPK3	ENST00000395199.7	TSL:1	c.1008G>A	p.Pro336Pro	synonymous	Exon 7 of 7	ENSP00000378625.3	P27361-3
	MAPK3	ENST00000395202.5	TSL:1	c.876G>A	p.Pro292Pro	synonymous	Exon 6 of 7	ENSP00000378628.1	P27361-2

Frequencies

GnomAD3 genomes AF: 0.00276 AC: 420 AN: 152090 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.00138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00694

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00188

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00301

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00311 AC: 780 AN: 250820 AF XY: 0.00318

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00420

Gnomad ASJ exome AF: 0.00528

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00217

Gnomad NFE exome AF: 0.00395

Gnomad OTH exome AF: 0.00638

GnomAD4 exome AF: 0.00274 AC: 3998 AN: 1461706 Hom.: 12 Cov.: 32 AF XY: 0.00274 AC XY: 1993 AN XY: 727140

African (AFR) AF: 0.00137 AC: 46 AN: 33478

American (AMR) AF: 0.00398 AC: 178 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00528 AC: 138 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00123 AC: 106 AN: 86226

European-Finnish (FIN) AF: 0.00300 AC: 160 AN: 53386

Middle Eastern (MID) AF: 0.0218 AC: 126 AN: 5768

European-Non Finnish (NFE) AF: 0.00274 AC: 3048 AN: 1111936

Other (OTH) AF: 0.00325 AC: 196 AN: 60384

GnomAD4 genome AF: 0.00275 AC: 418 AN: 152208 Hom.: 2 Cov.: 31 AF XY: 0.00280 AC XY: 208 AN XY: 74400

African (AFR) AF: 0.00135 AC: 56 AN: 41538

American (AMR) AF: 0.00693 AC: 106 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4830

European-Finnish (FIN) AF: 0.00188 AC: 20 AN: 10612

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00301 AC: 205 AN: 68002

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.00310 Hom.: 0

Bravo AF: 0.00295

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00420

EpiControl AF: 0.00367

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	MAPK3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.7
DANN	Benign	0.63
PhyloP100		-0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1143695; hg19: chr16-30128224;