GeneBe

chr5-56882021-TCAACAACAACAACAA-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005921.2(MAP3K1):​c.2833_2847delACAACAACAACAACA​(p.Thr945_Thr949del) variant causes a conservative inframe deletion change. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 0)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

MAP3K1
NM_005921.2 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.55

Publications

23 publications found
Variant links:
Genes affected
MAP3K1 (HGNC:6848): (mitogen-activated protein kinase kinase kinase 1) The protein encoded by this gene is a serine/threonine kinase and is part of some signal transduction cascades, including the ERK and JNK kinase pathways as well as the NF-kappa-B pathway. The encoded protein is activated by autophosphorylation and requires magnesium as a cofactor in phosphorylating other proteins. This protein has E3 ligase activity conferred by a plant homeodomain (PHD) in its N-terminus and phospho-kinase activity conferred by a kinase domain in its C-terminus. [provided by RefSeq, Mar 2012]
MAP3K1 Gene-Disease associations (from GenCC):
  • 46,XY sex reversal 6
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
  • breast cancer
    Inheritance: AD Classification: MODERATE Submitted by: G2P
  • 46,XY complete gonadal dysgenesis
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • 46,XY partial gonadal dysgenesis
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAP3K1NM_005921.2 linkc.2833_2847delACAACAACAACAACA p.Thr945_Thr949del conservative_inframe_deletion Exon 14 of 20 ENST00000399503.4 NP_005912.1 Q13233
MAP3K1XM_047417218.1 linkc.2833_2847delACAACAACAACAACA p.Thr945_Thr949del conservative_inframe_deletion Exon 14 of 18 XP_047273174.1
MAP3K1XM_047417219.1 linkc.2422_2436delACAACAACAACAACA p.Thr808_Thr812del conservative_inframe_deletion Exon 15 of 21 XP_047273175.1
MAP3K1XM_047417220.1 linkc.2422_2436delACAACAACAACAACA p.Thr808_Thr812del conservative_inframe_deletion Exon 15 of 21 XP_047273176.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAP3K1ENST00000399503.4 linkc.2833_2847delACAACAACAACAACA p.Thr945_Thr949del conservative_inframe_deletion Exon 14 of 20 1 NM_005921.2 ENSP00000382423.3 Q13233

Frequencies

GnomAD3 genomes
AF:
0.00000662
AC:
1
AN:
150946
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000660
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
Data not reliable, filtered out with message: AS_VQSR
AF:
7.04e-7
AC:
1
AN:
1421430
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
707624
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
32802
American (AMR)
AF:
0.0000226
AC:
1
AN:
44156
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25526
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39396
South Asian (SAS)
AF:
0.00
AC:
0
AN:
84488
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52274
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5658
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1078202
Other (OTH)
AF:
0.00
AC:
0
AN:
58928
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.00000662
AC:
1
AN:
150946
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
73616
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
40946
American (AMR)
AF:
0.0000660
AC:
1
AN:
15160
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3462
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5124
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4800
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10412
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67750
Other (OTH)
AF:
0.00
AC:
0
AN:
2076
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
4880

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
6.6
Mutation Taster
=161/39
polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs5868032; hg19: chr5-56177848; API