Variant 1-27356689-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004672.5(MAP3K6):c.3425A>G(p.Gln1142Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,609,052 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 30 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 17 hom. )

Consequence

MAP3K6
NM_004672.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.480

Variant links:

Genes affected

MAP3K6 (HGNC:6858): (mitogen-activated protein kinase kinase kinase 6) This gene encodes a serine/threonine protein kinase that forms a component of protein kinase-mediated signal transduction cascades. The encoded kinase participates in the regulation of vascular endothelial growth factor (VEGF) expression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

MAP3K6 links:

MAP3K6 (HGNC:):

MAP3K6 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 (MetaRNN=0.002960652).

BP6

Variant 1-27356689-T-C is Benign according to our data. Variant chr1-27356689-T-C is described in ClinVar as [Benign]. Clinvar id is 791784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0103 (1562/152344) while in subpopulation AFR AF= 0.0355 (1477/41568). AF 95% confidence interval is 0.034. There are 30 homozygotes in gnomad4. There are 756 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1562 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K6	NM_004672.5 linkuse as main transcript	c.3425A>G	p.Gln1142Arg	missense_variant	25/29	ENST00000357582.3	NP_004663.3	O95382-1
MAP3K6	NM_001297609.2 linkuse as main transcript	c.3401A>G	p.Gln1134Arg	missense_variant	24/28		NP_001284538.1	O95382-3
MAP3K6	XM_047433689.1 linkuse as main transcript	c.3332A>G	p.Gln1111Arg	missense_variant	26/30		XP_047289645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K6	ENST00000357582.3 linkuse as main transcript	c.3425A>G	p.Gln1142Arg	missense_variant	25/29	1	NM_004672.5	ENSP00000350195.2		O95382-1

Frequencies

GnomAD3 genomes

AF:

0.0102

AC:

1558

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0356

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00379

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00271

AC:

667

AN:

245946

Hom.:

AF XY:

0.00196

AC XY:

260

AN XY:

132972

show subpopulations

Gnomad AFR exome

AF:

0.0346

Gnomad AMR exome

AF:

0.00256

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000670

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000117

Gnomad OTH exome

AF:

0.00117

GnomAD4 exome

AF:

0.00104

AC:

1509

AN:

1456708

Hom.:

Cov.:

AF XY:

0.000893

AC XY:

647

AN XY:

724258

show subpopulations

Gnomad4 AFR exome

AF:

0.0338

Gnomad4 AMR exome

AF:

0.00301

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000586

Gnomad4 OTH exome

AF:

0.00264

GnomAD4 genome

AF:

0.0103

AC:

1562

AN:

152344

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

756

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.0355

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.00184

Hom.:

Bravo

AF:

0.0119

ESP6500AA

AF:

0.0318

AC:

140

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00318

AC:

386

Asia WGS

AF:

0.00260

AC:

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	Labcorp Genetics (formerly Invitae), Labcorp	Apr 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.60

CADD

Benign

5.8

DANN

Benign

0.71

DEOGEN2

Benign

0.034

.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.38

T;.;T

MetaRNN

Benign

0.0030

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

.;L;L

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.66

N;N;N

REVEL

Benign

0.049

Sift

Benign

0.22

T;T;T

Sift4G

Benign

0.48

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.088

MVP

0.19

MPC

0.33

ClinPred

0.00061

GERP RS

-0.22

Varity_R

0.045

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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