Variant chr16-84479954-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_020947.4(MEAK7):c.1330C>T(p.Arg444Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00323 in 1,609,612 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 16 hom. )

Consequence

MEAK7
NM_020947.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.62

Variant links:

Genes affected

MEAK7 (HGNC:29325): (MTOR associated protein, eak-7 homolog) Involved in several processes, including TOR signaling; positive regulation of protein localization to lysosome; and response to insulin. Located in cytosol; lysosomal membrane; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

MEAK7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0069999397).

BP6

Variant 16-84479954-G-A is Benign according to our data. Variant chr16-84479954-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 778506.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEAK7	NM_020947.4 linkuse as main transcript	c.1330C>T	p.Arg444Cys	missense_variant	8/8	ENST00000343629.11	NP_065998.3	Q6P9B6A8K5C2
MEAK7	XM_005256075.3 linkuse as main transcript	c.1330C>T	p.Arg444Cys	missense_variant	9/9		XP_005256132.1	Q6P9B6
MEAK7	XM_017023511.2 linkuse as main transcript	c.1330C>T	p.Arg444Cys	missense_variant	8/8		XP_016879000.1	Q6P9B6
MEAK7	XM_047434410.1 linkuse as main transcript	c.1330C>T	p.Arg444Cys	missense_variant	8/8		XP_047290366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEAK7	ENST00000343629.11 linkuse as main transcript	c.1330C>T	p.Arg444Cys	missense_variant	8/8	1	NM_020947.4	ENSP00000343635.6		Q6P9B6

Frequencies

GnomAD3 genomes

AF:

0.00268

AC:

408

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000989

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00103

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00439

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00255

AC:

635

AN:

249320

Hom.:

AF XY:

0.00266

AC XY:

359

AN XY:

134750

show subpopulations

Gnomad AFR exome

AF:

0.000869

Gnomad AMR exome

AF:

0.00202

Gnomad ASJ exome

AF:

0.00160

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.000231

Gnomad FIN exome

AF:

0.00139

Gnomad NFE exome

AF:

0.00426

Gnomad OTH exome

AF:

0.00264

GnomAD4 exome

AF:

0.00328

AC:

4783

AN:

1457266

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

2346

AN XY:

724684

show subpopulations

Gnomad4 AFR exome

AF:

0.000870

Gnomad4 AMR exome

AF:

0.00213

Gnomad4 ASJ exome

AF:

0.00180

Gnomad4 EAS exome

AF:

0.0000759

Gnomad4 SAS exome

AF:

0.000245

Gnomad4 FIN exome

AF:

0.00167

Gnomad4 NFE exome

AF:

0.00388

Gnomad4 OTH exome

AF:

0.00288

GnomAD4 genome

AF:

0.00268

AC:

408

AN:

152346

Hom.:

Cov.:

AF XY:

0.00272

AC XY:

203

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00103

Gnomad4 NFE

AF:

0.00440

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00372

Hom.:

Bravo

AF:

0.00277

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00372

AC:

ExAC

AF:

0.00237

AC:

288

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00519

EpiControl

AF:

0.00405

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.037

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.37

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0084

MetaRNN

Benign

0.0070

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-4.9

REVEL

Benign

0.022

Sift

Benign

0.078

Sift4G

Benign

0.20

Polyphen

0.080

Vest4

0.14

MVP

0.13

MPC

0.0017

ClinPred

0.024

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.40

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