Genetic Variant MAP3K19:p.Arg1007Lys (chr2-134985852-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_025052.5(MAP3K19):c.3020G>A(p.Arg1007Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,228 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1007T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

MAP3K19
NM_025052.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.340

Publications

0 publications found

Variant links:

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]

MAP3K19 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12382376).

BS2

High AC in GnomAdExome4 at 5 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAP3K19	NM_025052.5	MANE Select	c.3020G>A	p.Arg1007Lys	missense	Exon 10 of 13	NP_079328.3	Q56UN5-1
MAP3K19	NM_001400438.1		c.3020G>A	p.Arg1007Lys	missense	Exon 10 of 13	NP_001387367.1	Q56UN5-1
MAP3K19	NM_001018044.3		c.2681G>A	p.Arg894Lys	missense	Exon 5 of 8	NP_001018054.1	Q56UN5-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAP3K19	ENST00000392915.7	TSL:5 MANE Select	c.3020G>A	p.Arg1007Lys	missense	Exon 10 of 13	ENSP00000376647.2	Q56UN5-1
MAP3K19	ENST00000375845.8	TSL:1	c.3020G>A	p.Arg1007Lys	missense	Exon 7 of 10	ENSP00000365005.3	Q56UN5-1
MAP3K19	ENST00000358371.9	TSL:1	c.2681G>A	p.Arg894Lys	missense	Exon 5 of 8	ENSP00000351140.4	Q56UN5-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250624

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461228

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726844

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33434

American (AMR)

AF:

0.00

AC:

AN:

44618

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

86008

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111834

Other (OTH)

AF:

0.00

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000225

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

5.3

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.0034

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.38

M_CAP

Benign

0.031

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.76

PhyloP100

0.34

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.92

REVEL

Benign

0.072

Sift

Benign

0.092

Sift4G

Uncertain

0.021

Polyphen

0.0060

Vest4

0.046

MutPred

0.40

Gain of ubiquitination at R1007 (P = 0.0104)

MVP

0.37

MPC

0.12

ClinPred

0.079

GERP RS

0.065

Varity_R

0.071

gMVP

0.24

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over