Variant 16-84480545-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_020947.4(MEAK7):c.1241C>T(p.Pro414Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000201 in 1,611,568 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 3 hom. )

Consequence

MEAK7
NM_020947.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00550133).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MEAK7	NM_020947.4 linkuse as main transcript	c.1241C>T	p.Pro414Leu	missense_variant	7/8	ENST00000343629.11	NP_065998.3
MEAK7	XM_005256075.3 linkuse as main transcript	c.1241C>T	p.Pro414Leu	missense_variant	8/9		XP_005256132.1
MEAK7	XM_017023511.2 linkuse as main transcript	c.1241C>T	p.Pro414Leu	missense_variant	7/8		XP_016879000.1
MEAK7	XM_047434410.1 linkuse as main transcript	c.1241C>T	p.Pro414Leu	missense_variant	7/8		XP_047290366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MEAK7	ENST00000343629.11 linkuse as main transcript	c.1241C>T	p.Pro414Leu	missense_variant	7/8	1	NM_020947.4	ENSP00000343635	P1
MEAK7	ENST00000566995.5 linkuse as main transcript	c.*655C>T		3_prime_UTR_variant, NMD_transcript_variant	8/9	5		ENSP00000454265
MEAK7	ENST00000570036.5 linkuse as main transcript	c.*1296C>T		3_prime_UTR_variant, NMD_transcript_variant	8/9	2		ENSP00000455332

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000357

AC:

AN:

249098

Hom.:

AF XY:

0.000290

AC XY:

AN XY:

134596

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00730

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000116

Gnomad OTH exome

AF:

0.000659

GnomAD4 exome

AF:

0.000201

AC:

294

AN:

1459398

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

140

AN XY:

725964

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00829

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000405

Gnomad4 OTH exome

AF:

0.000548

GnomAD4 genome

AF:

0.000197

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000387

Hom.:

Bravo

AF:

0.000215

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000338

AC:

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

Jul 14, 2021

The c.1241C>T (p.P414L) alteration is located in exon 7 (coding exon 6) of the TLDC1 gene. This alteration results from a C to T substitution at nucleotide position 1241, causing the proline (P) at amino acid position 414 to be replaced by a leucine (L). 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

0.071

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.3

DANN

Benign

0.13

DEOGEN2

Benign

0.0060

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.71

M_CAP

Benign

0.0096

MetaRNN

Benign

0.0055

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.66

REVEL

Benign

0.067

Sift

Benign

0.76

Sift4G

Benign

0.83

Polyphen

0.0010

Vest4

0.080

MVP

0.055

MPC

0.0021

ClinPred

0.0061

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.021

gMVP

0.39

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