Variant 14-50438003-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006575.6(MAP4K5):c.1714A>C(p.Thr572Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,421,584 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MAP4K5
NM_006575.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.83

Variant links:

Genes affected

MAP4K5 (HGNC:6867): (mitogen-activated protein kinase kinase kinase kinase 5) This gene encodes a member of the serine/threonine protein kinase family, that is highly similar to yeast SPS1/STE20 kinase. Yeast SPS1/STE20 functions near the beginning of the MAP kinase signal cascades that is essential for yeast pheromone response. This kinase was shown to activate Jun kinase in mammalian cells, which suggested a role in stress response. Two alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Jul 2008]

MAP4K5 links:

MAP4K5 (HGNC:):

MAP4K5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP4K5	NM_006575.6 linkuse as main transcript	c.1714A>C	p.Thr572Pro	missense_variant	25/33	ENST00000682126.1	NP_006566.2	Q9Y4K4A0A804HIS2B3KWC4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP4K5	ENST00000682126.1 linkuse as main transcript	c.1714A>C	p.Thr572Pro	missense_variant	25/33		NM_006575.6	ENSP00000507200.1		A0A804HIS2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246342

Hom.:

AF XY:

0.00000749

AC XY:

AN XY:

133528

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000894

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1421584

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

709646

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000186

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

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

Aug 26, 2024

The c.1714A>C (p.T572P) alteration is located in exon 25 (coding exon 24) of the MAP4K5 gene. This alteration results from a A to C substitution at nucleotide position 1714, causing the threonine (T) at amino acid position 572 to be replaced by a proline (P). 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

0.21

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.098

MetaRNN

Uncertain

0.58

MetaSVM

Uncertain

0.16

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.62

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.47

MutPred

0.50

Gain of catalytic residue at K571 (P = 0);

MVP

0.74

MPC

0.92

ClinPred

0.95

GERP RS

5.2

Varity_R

0.71

gMVP

0.59

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