16-30116903-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002746.3(MAPK3):​c.1008G>T​(p.Pro336Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P336P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MAPK3 NM_002746.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=-0.48 with no splicing effect.

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>T	p.Pro336Pro	synonymous	Exon 7 of 9	NP_002737.2	L7RXH5
	MAPK3	NM_001040056.3		c.1008G>T	p.Pro336Pro	synonymous	Exon 7 of 7	NP_001035145.1	P27361-3
	MAPK3	NM_001109891.2		c.876G>T	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>T	p.Pro336Pro	synonymous	Exon 7 of 9	ENSP00000263025.4	P27361-1
	MAPK3	ENST00000395199.7	TSL:1	c.1008G>T	p.Pro336Pro	synonymous	Exon 7 of 7	ENSP00000378625.3	P27361-3
	MAPK3	ENST00000395202.5	TSL:1	c.876G>T	p.Pro292Pro	synonymous	Exon 6 of 7	ENSP00000378628.1	P27361-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461712 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727144

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111938

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.1
DANN	Benign	0.59
PhyloP100		-0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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;