Variant chr21-29149212-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001286620.2(MAP3K7CL):c.94A>T(p.Ile32Phe) 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 1,613,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

MAP3K7CL
NM_001286620.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.779

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06011516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP3K7CL	NM_001286620.2 linkuse as main transcript	c.94A>T	p.Ile32Phe	missense_variant	3/5	ENST00000399928.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP3K7CL	ENST00000399928.6 linkuse as main transcript	c.94A>T	p.Ile32Phe	missense_variant	3/5	1	NM_001286620.2	P1	P57077-4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461690

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727178

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:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

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

Apr 23, 2024

The c.394A>T (p.I132F) alteration is located in exon 7 (coding exon 5) of the MAP3K7CL gene. This alteration results from a A to T substitution at nucleotide position 394, causing the isoleucine (I) at amino acid position 132 to be replaced by a phenylalanine (F). 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

0.072

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

6.9

DANN

Benign

0.90

DEOGEN2

Benign

0.023

T;.;.;T;T;.;.;.;.;.;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.67

.;.;.;.;T;.;T;.;.;T;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.060

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.20

N;.;.;N;N;.;.;.;.;.;.

MutationTaster

Benign

0.54

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

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.6

N;N;N;N;.;N;N;N;N;N;N

REVEL

Benign

0.017

Sift

Benign

0.068

T;T;T;T;.;T;T;T;T;T;T

Sift4G

Benign

0.21

T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.0010

B;.;.;B;B;.;.;.;.;.;.

Vest4

0.25

MVP

0.085

MPC

0.45

ClinPred

0.11

GERP RS

2.1

Varity_R

0.089

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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