Variant 1-27356738-CCTT-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PM4_SupportingBP6_ModerateBS2

The NM_004672.5(MAP3K6):c.3373_3375delAAG(p.Lys1125del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,565,996 control chromosomes in the GnomAD database, including 130 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0081 ( 7 hom., cov: 33)

Exomes 𝑓: 0.011 ( 123 hom. )

Consequence

MAP3K6
NM_004672.5 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.219

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 Likely_benign. Variant got -5 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_004672.5. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 1-27356738-CCTT-C is Benign according to our data. Variant chr1-27356738-CCTT-C is described in ClinVar as [Benign]. Clinvar id is 2638557.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 1229 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K6	NM_004672.5 linkuse as main transcript	c.3373_3375delAAG	p.Lys1125del	conservative_inframe_deletion	25/29	ENST00000357582.3	NP_004663.3	O95382-1
MAP3K6	NM_001297609.2 linkuse as main transcript	c.3349_3351delAAG	p.Lys1117del	conservative_inframe_deletion	24/28		NP_001284538.1	O95382-3
MAP3K6	XM_047433689.1 linkuse as main transcript	c.3280_3282delAAG	p.Lys1094del	conservative_inframe_deletion	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.3373_3375delAAG	p.Lys1125del	conservative_inframe_deletion	25/29	1	NM_004672.5	ENSP00000350195.2		O95382-1

Frequencies

GnomAD3 genomes

AF:

0.00807

AC:

1229

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00229

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00608

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00942

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0129

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00763

AC:

1596

AN:

209300

Hom.:

AF XY:

0.00799

AC XY:

893

AN XY:

111802

show subpopulations

Gnomad AFR exome

AF:

0.00145

Gnomad AMR exome

AF:

0.00369

Gnomad ASJ exome

AF:

0.0130

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00203

Gnomad FIN exome

AF:

0.00696

Gnomad NFE exome

AF:

0.0123

Gnomad OTH exome

AF:

0.00709

GnomAD4 exome

AF:

0.0112

AC:

15821

AN:

1413666

Hom.:

123

AF XY:

0.0110

AC XY:

7703

AN XY:

698468

show subpopulations

Gnomad4 AFR exome

AF:

0.00169

Gnomad4 AMR exome

AF:

0.00390

Gnomad4 ASJ exome

AF:

0.0109

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00241

Gnomad4 FIN exome

AF:

0.00701

Gnomad4 NFE exome

AF:

0.0131

Gnomad4 OTH exome

AF:

0.00862

GnomAD4 genome

AF:

0.00807

AC:

1229

AN:

152330

Hom.:

Cov.:

AF XY:

0.00772

AC XY:

575

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00229

Gnomad4 AMR

AF:

0.00607

Gnomad4 ASJ

AF:

0.0110

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00942

Gnomad4 NFE

AF:

0.0129

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00975

Hom.:

Bravo

AF:

0.00784

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

MAP3K6: PM4:Supporting, BS1, BS2 -

MAP3K6-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 26, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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