Variant 1-233353961-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_032435.3(MAP3K21):c.1135+6G>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,420,880 control chromosomes in the GnomAD database, including 118,783 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 15092 hom., cov: 32)

Exomes 𝑓: 0.44 ( 103691 hom. )

Consequence

MAP3K21
NM_032435.3 splice_donor_region, intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.490

Variant links:

Genes affected

MAP3K21 (HGNC:29798): (mitogen-activated protein kinase kinase kinase 21) Predicted to enable protein homodimerization activity and protein kinase activity. Predicted to be involved in protein autophosphorylation and signal transduction. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MAP3K21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-233353961-G-T is Benign according to our data. Variant chr1-233353961-G-T is described in ClinVar as [Benign]. Clinvar id is 767764.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP3K21	NM_032435.3 linkuse as main transcript	c.1135+6G>T		splice_donor_region_variant, intron_variant		ENST00000366624.8	NP_115811.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP3K21	ENST00000366624.8 linkuse as main transcript	c.1135+6G>T		splice_donor_region_variant, intron_variant		1	NM_032435.3	ENSP00000355583	P2	Q5TCX8-1
MAP3K21	ENST00000366623.7 linkuse as main transcript	c.1135+6G>T		splice_donor_region_variant, intron_variant		1		ENSP00000355582	A2	Q5TCX8-2

Frequencies

GnomAD3 genomes

AF:

0.441

AC:

66713

AN:

151292

Hom.:

15055

Cov.:

show subpopulations

Gnomad AFR

AF:

0.487

Gnomad AMI

AF:

0.383

Gnomad AMR

AF:

0.554

Gnomad ASJ

AF:

0.356

Gnomad EAS

AF:

0.524

Gnomad SAS

AF:

0.467

Gnomad FIN

AF:

0.387

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.394

Gnomad OTH

AF:

0.423

GnomAD3 exomes

AF:

0.542

AC:

100085

AN:

184532

Hom.:

23009

AF XY:

0.538

AC XY:

53413

AN XY:

99214

show subpopulations

Gnomad AFR exome

AF:

0.567

Gnomad AMR exome

AF:

0.700

Gnomad ASJ exome

AF:

0.462

Gnomad EAS exome

AF:

0.586

Gnomad SAS exome

AF:

0.570

Gnomad FIN exome

AF:

0.472

Gnomad NFE exome

AF:

0.498

Gnomad OTH exome

AF:

0.516

GnomAD4 exome

AF:

0.439

AC:

556859

AN:

1269478

Hom.:

103691

Cov.:

AF XY:

0.442

AC XY:

276833

AN XY:

626708

show subpopulations

Gnomad4 AFR exome

AF:

0.512

Gnomad4 AMR exome

AF:

0.652

Gnomad4 ASJ exome

AF:

0.418

Gnomad4 EAS exome

AF:

0.600

Gnomad4 SAS exome

AF:

0.511

Gnomad4 FIN exome

AF:

0.446

Gnomad4 NFE exome

AF:

0.418

Gnomad4 OTH exome

AF:

0.449

GnomAD4 genome

AF:

0.441

AC:

66804

AN:

151402

Hom.:

15092

Cov.:

AF XY:

0.443

AC XY:

32735

AN XY:

73918

show subpopulations

Gnomad4 AFR

AF:

0.487

Gnomad4 AMR

AF:

0.555

Gnomad4 ASJ

AF:

0.356

Gnomad4 EAS

AF:

0.525

Gnomad4 SAS

AF:

0.468

Gnomad4 FIN

AF:

0.387

Gnomad4 NFE

AF:

0.394

Gnomad4 OTH

AF:

0.427

Alfa

AF:

0.421

Hom.:

3238

Bravo

AF:

0.451

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	Aug 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.8

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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