Variant 19-38605651-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001042600.3(MAP4K1):c.1280G>A(p.Arg427Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000686 in 1,603,234 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 (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

MAP4K1
NM_001042600.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15939382).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAP4K1	NM_001042600.3 linkuse as main transcript	c.1280G>A	p.Arg427Gln	missense_variant	18/31	ENST00000396857.7	NP_001036065.1
MAP4K1	NM_007181.6 linkuse as main transcript	c.1280G>A	p.Arg427Gln	missense_variant	18/32		NP_009112.1
MAP4K1	XM_011526404.2 linkuse as main transcript	c.1400G>A	p.Arg467Gln	missense_variant	19/32		XP_011524706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP4K1	ENST00000396857.7 linkuse as main transcript	c.1280G>A	p.Arg427Gln	missense_variant	18/31	5	NM_001042600.3	ENSP00000380066	P1	Q92918-2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000100

AC:

AN:

230058

Hom.:

AF XY:

0.0000944

AC XY:

AN XY:

127152

show subpopulations

Gnomad AFR exome

AF:

0.0000742

Gnomad AMR exome

AF:

0.0000325

Gnomad ASJ exome

AF:

0.000216

Gnomad EAS exome

AF:

0.0000585

Gnomad SAS exome

AF:

0.000410

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000384

Gnomad OTH exome

AF:

0.000357

GnomAD4 exome

AF:

0.0000703

AC:

102

AN:

1450970

Hom.:

Cov.:

AF XY:

0.0000762

AC XY:

AN XY:

721822

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.0000241

Gnomad4 ASJ exome

AF:

0.000312

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000447

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000415

Gnomad4 OTH exome

AF:

0.000134

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000710

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.000100

AC:

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 16, 2023

The c.1280G>A (p.R427Q) alteration is located in exon 18 (coding exon 18) of the MAP4K1 gene. This alteration results from a G to A substitution at nucleotide position 1280, causing the arginine (R) at amino acid position 427 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.36

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.25

T;T;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Benign

0.52

M_CAP

Benign

0.055

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.7

M;.;M

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.7

.;.;N

REVEL

Benign

0.096

Sift

Uncertain

0.012

.;.;D

Sift4G

Benign

0.13

T;T;T

Polyphen

1.0

D;.;D

Vest4

0.30

MutPred

0.39

Loss of sheet (P = 0.0457);.;Loss of sheet (P = 0.0457);

MVP

0.43

MPC

0.85

ClinPred

0.39

GERP RS

5.2

Varity_R

0.30

gMVP

0.45

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over