Variant chr21-29092560-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000341618.8(MAP3K7CL):c.349G>A(p.Glu117Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000044 in 1,614,140 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000046 ( 1 hom. )

Consequence

MAP3K7CL
ENST00000341618.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.49

Variant links:

Genes affected

MAP3K7CL (HGNC:16457): (MAP3K7 C-terminal like) Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MAP3K7CL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27126166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
MAP3K7CL	NM_001286634.2 linkuse as main transcript	c.349G>A	p.Glu117Lys	missense_variant	5/8
MAP3K7CL	NM_001371369.1 linkuse as main transcript	c.349G>A	p.Glu117Lys	missense_variant	6/9
MAP3K7CL	NM_020152.4 linkuse as main transcript	c.349G>A	p.Glu117Lys	missense_variant	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	UniProt
MAP3K7CL	ENST00000341618.8 linkuse as main transcript	c.349G>A	p.Glu117Lys	missense_variant	5/8	1	P57077-1
MAP3K7CL	ENST00000399947.6 linkuse as main transcript	c.349G>A	p.Glu117Lys	missense_variant	6/9	1	P57077-1
MAP3K7CL	ENST00000496779.5 linkuse as main transcript	n.797G>A		non_coding_transcript_exon_variant	6/7	1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152186

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:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000676

AC:

AN:

251488

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

135916

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:

0.000555

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000458

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.0000715

AC XY:

AN XY:

727198

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:

0.000707

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74478

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:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.000107

AC:

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

Jun 05, 2024

The c.349G>A (p.E117K) alteration is located in exon 6 (coding exon 4) of the MAP3K7CL gene. This alteration results from a G to A substitution at nucleotide position 349, causing the glutamic acid (E) at amino acid position 117 to be replaced by a lysine (K). 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

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0083

T;T;T

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.49

.;.;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

0.55

N;N;N

MutationTaster

Benign

1.0

D;D;D;D;N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.23

N;N;D

REVEL

Benign

0.25

Sift

Benign

0.35

T;T;D

Sift4G

Benign

0.39

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.56

MutPred

0.26

Gain of methylation at E117 (P = 0.0022);Gain of methylation at E117 (P = 0.0022);Gain of methylation at E117 (P = 0.0022);

MVP

0.46

MPC

0.34

ClinPred

0.36

GERP RS

4.3

Varity_R

0.27

gMVP

0.088

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