Variant chr17-63632869-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002401.5(MAP3K3):c.126+67G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 1,597,856 control chromosomes in the GnomAD database, including 657 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 256 hom., cov: 31)

Exomes 𝑓: 0.016 ( 401 hom. )

Consequence

MAP3K3
NM_002401.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.802

Variant links:

Genes affected

MAP3K3 (HGNC:6855): (mitogen-activated protein kinase kinase kinase 3) This gene product is a 626-amino acid polypeptide that is 96.5% identical to mouse Mekk3. Its catalytic domain is closely related to those of several other kinases, including mouse Mekk2, tobacco NPK, and yeast Ste11. Northern blot analysis revealed a 4.6-kb transcript that appears to be ubiquitously expressed. This protein directly regulates the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by activating SEK and MEK1/2 respectively; it does not regulate the p38 pathway. In cotransfection assays, it enhanced transcription from a nuclear factor kappa-B (NFKB)-dependent reporter gene, consistent with a role in the SAPK pathway. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

MAP3K3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 17-63632869-G-T is Benign according to our data. Variant chr17-63632869-G-T is described in ClinVar as [Benign]. Clinvar id is 1221866.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0995 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K3	NM_002401.5 linkuse as main transcript	c.126+67G>T		intron_variant		ENST00000361733.8	NP_002392.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K3	ENST00000361733.8 linkuse as main transcript	c.126+67G>T		intron_variant		1	NM_002401.5	ENSP00000354485	A1	Q99759-1

Frequencies

GnomAD3 genomes

AF:

0.0402

AC:

6112

AN:

152108

Hom.:

257

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0391

Gnomad ASJ

AF:

0.0236

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0282

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0137

Gnomad OTH

AF:

0.0436

GnomAD4 exome

AF:

0.0162

AC:

23460

AN:

1445630

Hom.:

401

AF XY:

0.0164

AC XY:

11797

AN XY:

719048

show subpopulations

Gnomad4 AFR exome

AF:

0.112

Gnomad4 AMR exome

AF:

0.0208

Gnomad4 ASJ exome

AF:

0.0219

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0257

Gnomad4 FIN exome

AF:

0.00322

Gnomad4 NFE exome

AF:

0.0131

Gnomad4 OTH exome

AF:

0.0220

GnomAD4 genome

AF:

0.0402

AC:

6113

AN:

152226

Hom.:

256

Cov.:

AF XY:

0.0388

AC XY:

2889

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.0390

Gnomad4 ASJ

AF:

0.0236

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0280

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.0136

Gnomad4 OTH

AF:

0.0432

Alfa

AF:

0.00595

Hom.:

Bravo

AF:

0.0458

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

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