Variant 16-84479936-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020947.4(MEAK7):c.1348C>T(p.Arg450Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000028 in 1,609,228 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

MEAK7
NM_020947.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.66

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MEAK7	NM_020947.4 linkuse as main transcript	c.1348C>T	p.Arg450Trp	missense_variant	8/8	ENST00000343629.11	NP_065998.3
MEAK7	XM_005256075.3 linkuse as main transcript	c.1348C>T	p.Arg450Trp	missense_variant	9/9		XP_005256132.1
MEAK7	XM_017023511.2 linkuse as main transcript	c.1348C>T	p.Arg450Trp	missense_variant	8/8		XP_016879000.1
MEAK7	XM_047434410.1 linkuse as main transcript	c.1348C>T	p.Arg450Trp	missense_variant	8/8		XP_047290366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MEAK7	ENST00000343629.11 linkuse as main transcript	c.1348C>T	p.Arg450Trp	missense_variant	8/8	1	NM_020947.4	ENSP00000343635	P1
MEAK7	ENST00000566995.5 linkuse as main transcript	c.*762C>T		3_prime_UTR_variant, NMD_transcript_variant	9/9	5		ENSP00000454265
MEAK7	ENST00000570036.5 linkuse as main transcript	c.*1403C>T		3_prime_UTR_variant, NMD_transcript_variant	9/9	2		ENSP00000455332

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000521

AC:

AN:

249650

Hom.:

AF XY:

0.0000445

AC XY:

AN XY:

134976

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000875

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000709

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000268

AC:

AN:

1456892

Hom.:

Cov.:

AF XY:

0.0000235

AC XY:

AN XY:

724078

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000673

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000280

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

The c.1348C>T (p.R450W) alteration is located in exon 8 (coding exon 7) of the TLDC1 gene. This alteration results from a C to T substitution at nucleotide position 1348, causing the arginine (R) at amino acid position 450 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.066

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.051

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.039

MetaRNN

Uncertain

0.65

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-6.5

REVEL

Uncertain

0.31

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.62

MutPred

0.51

Gain of catalytic residue at P453 (P = 0.0281);

MVP

0.26

MPC

0.0064

ClinPred

0.95

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.41

gMVP

0.66

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