dbSNP rs1042030777: MAP4K1:p.Ala452Val (chr19-38605576-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001042600.3(MAP4K1):c.1355C>T(p.Ala452Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000123 in 1,541,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A452T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

MAP4K1
NM_001042600.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.08

Publications

0 publications found

Variant links:

Genes affected

MAP4K1 (HGNC:6863): (mitogen-activated protein kinase kinase kinase kinase 1) Enables ATP binding activity and MAP kinase kinase kinase kinase activity. Involved in several processes, including JNK cascade; cellular response to phorbol 13-acetate 12-myristate; and protein phosphorylation. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

MAP4K1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21207526).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042600.3. 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
	MAP4K1	NM_001042600.3	MANE Select	c.1355C>T	p.Ala452Val	missense	Exon 18 of 31	NP_001036065.1	Q92918-2
	MAP4K1	NM_007181.6		c.1355C>T	p.Ala452Val	missense	Exon 18 of 32	NP_009112.1	Q92918-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAP4K1	ENST00000396857.7	TSL:5 MANE Select	c.1355C>T	p.Ala452Val	missense	Exon 18 of 31	ENSP00000380066.1	Q92918-2
MAP4K1	ENST00000591517.5	TSL:1	c.1355C>T	p.Ala452Val	missense	Exon 18 of 32	ENSP00000465039.1	Q92918-1
MAP4K1	ENST00000864511.1		c.1475C>T	p.Ala492Val	missense	Exon 19 of 32	ENSP00000534570.1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000694

AC:

AN:

144188

AF XY:

0.0000127

show subpopulations

Gnomad AFR exome

AF:

0.000133

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000216

AC:

AN:

1389002

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

686414

show subpopulations

African (AFR)

AF:

0.0000972

AC:

AN:

30872

American (AMR)

AF:

0.00

AC:

AN:

30064

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24072

East Asian (EAS)

AF:

0.00

AC:

AN:

36504

South Asian (SAS)

AF:

0.00

AC:

AN:

78896

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48202

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5480

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1077500

Other (OTH)

AF:

0.00

AC:

AN:

57412

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000105

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.000386

AC:

AN:

41406

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Benign

0.46

M_CAP

Uncertain

0.096

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.2

PhyloP100

4.1

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.3

REVEL

Benign

0.074

Sift

Benign

0.23

Sift4G

Benign

0.24

Polyphen

0.77

Vest4

0.28

MutPred

0.19

Gain of glycosylation at S454 (P = 0.18)

MVP

0.76

MPC

0.31

ClinPred

0.25

GERP RS

5.2

Varity_R

0.088

gMVP

0.23

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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