Variant 19-38607886-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.1135G>A(p.Asp379Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,611,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

MAP4K1
NM_001042600.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.21

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=0.1315285).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAP4K1	NM_001042600.3 linkuse as main transcript	c.1135G>A	p.Asp379Asn	missense_variant	16/31	ENST00000396857.7	NP_001036065.1
MAP4K1	NM_007181.6 linkuse as main transcript	c.1135G>A	p.Asp379Asn	missense_variant	16/32		NP_009112.1
MAP4K1	XM_011526404.2 linkuse as main transcript	c.1135G>A	p.Asp379Asn	missense_variant	16/32		XP_011524706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP4K1	ENST00000396857.7 linkuse as main transcript	c.1135G>A	p.Asp379Asn	missense_variant	16/31	5	NM_001042600.3	ENSP00000380066	P1	Q92918-2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1459982

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726100

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151996

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Dec 27, 2022

The c.1135G>A (p.D379N) alteration is located in exon 16 (coding exon 16) of the MAP4K1 gene. This alteration results from a G to A substitution at nucleotide position 1135, causing the aspartic acid (D) at amino acid position 379 to be replaced by an asparagine (N). 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

0.088

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;T;.

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.81

M_CAP

Benign

0.065

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.5

L;.;L

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.38

.;.;N

REVEL

Benign

0.026

Sift

Benign

0.23

.;.;T

Sift4G

Benign

0.37

T;T;T

Polyphen

0.013

B;.;B

Vest4

0.19

MutPred

0.21

Gain of relative solvent accessibility (P = 0.0479);.;Gain of relative solvent accessibility (P = 0.0479);

MVP

0.75

MPC

0.74

ClinPred

0.70

GERP RS

3.3

Varity_R

0.047

gMVP

0.30

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