16-30117160-A-G

Variant names:

• chr16-30117160-A-G
• rs757561553
• NM_002746.3:c.901T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_002746.3(MAPK3):​c.901T>C​(p.Ser301Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: MAPK3 NM_002746.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.562
• Publications: 2 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07417214).
• BP6: Variant 16-30117160-A-G is Benign according to our data. Variant chr16-30117160-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3870435.Status of the report is criteria_provided_single_submitter, 1 stars.

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.901T>C	p.Ser301Pro	missense	Exon 6 of 9	NP_002737.2	L7RXH5
	MAPK3	NM_001040056.3		c.901T>C	p.Ser301Pro	missense	Exon 6 of 7	NP_001035145.1	P27361-3
	MAPK3	NM_001109891.2		c.776-157T>C		intron	N/A	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.901T>C	p.Ser301Pro	missense	Exon 6 of 9	ENSP00000263025.4	P27361-1
	MAPK3	ENST00000395199.7	TSL:1	c.901T>C	p.Ser301Pro	missense	Exon 6 of 7	ENSP00000378625.3	P27361-3
	MAPK3	ENST00000484663.5	TSL:1	c.559T>C	p.Ser187Pro	missense	Exon 5 of 8	ENSP00000432742.1	A1QJE5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251362 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461842 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111990

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.71
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.54	N
PhyloP100		0.56
PrimateAI	Benign	0.43	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.11
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.55		Gain of glycosylation at S301 (P = 0.0683)
MVP		0.65
MPC		0.82
ClinPred		0.065	T
GERP RS		0.82
Varity_R		0.43
gMVP		0.50
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs757561553; hg19: chr16-30128481;