Variant 16-84479983-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_020947.4(MEAK7):c.1301A>G(p.Gln434Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000863 in 1,609,274 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q434H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0049 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00044 ( 1 hom. )

Consequence

MEAK7
NM_020947.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.687

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003116101).

BP6

Variant 16-84479983-T-C is Benign according to our data. Variant chr16-84479983-T-C is described in ClinVar as [Benign]. Clinvar id is 707958.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00493 (751/152318) while in subpopulation AFR AF= 0.0168 (697/41582). AF 95% confidence interval is 0.0157. There are 5 homozygotes in gnomad4. There are 343 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MEAK7	NM_020947.4 linkuse as main transcript	c.1301A>G	p.Gln434Arg	missense_variant	8/8	ENST00000343629.11
MEAK7	XM_005256075.3 linkuse as main transcript	c.1301A>G	p.Gln434Arg	missense_variant	9/9
MEAK7	XM_017023511.2 linkuse as main transcript	c.1301A>G	p.Gln434Arg	missense_variant	8/8
MEAK7	XM_047434410.1 linkuse as main transcript	c.1301A>G	p.Gln434Arg	missense_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MEAK7	ENST00000343629.11 linkuse as main transcript	c.1301A>G	p.Gln434Arg	missense_variant	8/8	1	NM_020947.4	P1
MEAK7	ENST00000566995.5 linkuse as main transcript	c.*715A>G		3_prime_UTR_variant, NMD_transcript_variant	9/9	5
MEAK7	ENST00000570036.5 linkuse as main transcript	c.*1356A>G		3_prime_UTR_variant, NMD_transcript_variant	9/9	2

Frequencies

GnomAD3 genomes

AF:

0.00493

AC:

751

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0168

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00131

AC:

325

AN:

248992

Hom.:

AF XY:

0.000988

AC XY:

133

AN XY:

134632

show subpopulations

Gnomad AFR exome

AF:

0.0180

Gnomad AMR exome

AF:

0.000705

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000443

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.000437

AC:

637

AN:

1456956

Hom.:

Cov.:

AF XY:

0.000380

AC XY:

275

AN XY:

724494

show subpopulations

Gnomad4 AFR exome

AF:

0.0154

Gnomad4 AMR exome

AF:

0.00106

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.000998

GnomAD4 genome

AF:

0.00493

AC:

751

AN:

152318

Hom.:

Cov.:

AF XY:

0.00461

AC XY:

343

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0168

Gnomad4 AMR

AF:

0.00274

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00101

Hom.:

Bravo

AF:

0.00642

ESP6500AA

AF:

0.0191

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00171

AC:

208

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000547

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.2

DANN

Benign

0.60

DEOGEN2

Benign

0.0013

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.64

MetaRNN

Benign

0.0031

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.73

MutationTaster

Benign

0.64

D;D

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.70

REVEL

Benign

0.037

Sift

Benign

0.45

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.046

MVP

0.040

MPC

0.0021

ClinPred

0.0044

GERP RS

-4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.019

gMVP

0.55

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