Variant 17-63632650-G-A 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.5-31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,611,010 control chromosomes in the GnomAD database, including 73,735 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 14316 hom., cov: 32)

Exomes 𝑓: 0.27 ( 59419 hom. )

Consequence

MAP3K3
NM_002401.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.488

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=-0.87).

BP6

Variant 17-63632650-G-A is Benign according to our data. Variant chr17-63632650-G-A is described in ClinVar as [Benign]. Clinvar id is 1271201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.704 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.5-31G>A		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.5-31G>A		intron_variant		1	NM_002401.5	ENSP00000354485	A1	Q99759-1

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57604

AN:

151960

Hom.:

14263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.710

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.281

Gnomad EAS

AF:

0.0555

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.206

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.349

GnomAD3 exomes

AF:

0.265

AC:

66222

AN:

249778

Hom.:

11152

AF XY:

0.257

AC XY:

34664

AN XY:

135124

show subpopulations

Gnomad AFR exome

AF:

0.720

Gnomad AMR exome

AF:

0.219

Gnomad ASJ exome

AF:

0.280

Gnomad EAS exome

AF:

0.0469

Gnomad SAS exome

AF:

0.176

Gnomad FIN exome

AF:

0.218

Gnomad NFE exome

AF:

0.281

Gnomad OTH exome

AF:

0.258

GnomAD4 exome

AF:

0.272

AC:

396396

AN:

1458932

Hom.:

59419

Cov.:

AF XY:

0.268

AC XY:

194625

AN XY:

725966

show subpopulations

Gnomad4 AFR exome

AF:

0.727

Gnomad4 AMR exome

AF:

0.224

Gnomad4 ASJ exome

AF:

0.280

Gnomad4 EAS exome

AF:

0.0506

Gnomad4 SAS exome

AF:

0.179

Gnomad4 FIN exome

AF:

0.224

Gnomad4 NFE exome

AF:

0.277

Gnomad4 OTH exome

AF:

0.273

GnomAD4 genome

AF:

0.379

AC:

57701

AN:

152078

Hom.:

14316

Cov.:

AF XY:

0.370

AC XY:

27497

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.711

Gnomad4 AMR

AF:

0.248

Gnomad4 ASJ

AF:

0.281

Gnomad4 EAS

AF:

0.0557

Gnomad4 SAS

AF:

0.166

Gnomad4 FIN

AF:

0.206

Gnomad4 NFE

AF:

0.281

Gnomad4 OTH

AF:

0.345

Alfa

AF:

0.285

Hom.:

11406

Bravo

AF:

0.398

Asia WGS

AF:

0.163

AC:

570

AN:

3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.3

DANN

Benign

0.72

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