MAP3K19 p.Gln1309His

Variant names:

• chr2-134964910-C-A
• NM_025052.5:c.3927G>T
• MAP3K19 p.Gln1309His

Your query was ambiguous. Multiple possible variants found:

• chr2-134964910-C-A
• chr2-134964910-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_025052.5(MAP3K19):​c.3927G>T​(p.Gln1309His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAP3K19 NM_025052.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587
• Publications: 0 publications found

Genes affected

MAP3K19 (HGNC:26249): (mitogen-activated protein kinase kinase kinase 19) Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Predicted to be involved in protein phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30562437).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025052.5. 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
	MAP3K19	NM_025052.5	MANE Select	c.3927G>T	p.Gln1309His	missense	Exon 13 of 13	NP_079328.3	Q56UN5-1
	MAP3K19	NM_001400438.1		c.3927G>T	p.Gln1309His	missense	Exon 13 of 13	NP_001387367.1	Q56UN5-1
	MAP3K19	NM_001018044.3		c.3588G>T	p.Gln1196His	missense	Exon 8 of 8	NP_001018054.1	Q56UN5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP3K19	ENST00000392915.7	TSL:5 MANE Select	c.3927G>T	p.Gln1309His	missense	Exon 13 of 13	ENSP00000376647.2	Q56UN5-1
	MAP3K19	ENST00000375845.8	TSL:1	c.3927G>T	p.Gln1309His	missense	Exon 10 of 10	ENSP00000365005.3	Q56UN5-1
	MAP3K19	ENST00000358371.9	TSL:1	c.3588G>T	p.Gln1196His	missense	Exon 8 of 8	ENSP00000351140.4	Q56UN5-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.21	N
PhyloP100		0.59
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.26
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.017	D
Varity_R		0.32
gMVP		0.55
Mutation Taster		=70/30	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-135722480;