Variant 16-84480010-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020947.4(MEAK7):c.1274G>A(p.Ser425Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,603,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MEAK7
NM_020947.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.40

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24263877).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MEAK7	NM_020947.4 linkuse as main transcript	c.1274G>A	p.Ser425Asn	missense_variant	8/8	ENST00000343629.11	NP_065998.3
MEAK7	XM_005256075.3 linkuse as main transcript	c.1274G>A	p.Ser425Asn	missense_variant	9/9		XP_005256132.1
MEAK7	XM_017023511.2 linkuse as main transcript	c.1274G>A	p.Ser425Asn	missense_variant	8/8		XP_016879000.1
MEAK7	XM_047434410.1 linkuse as main transcript	c.1274G>A	p.Ser425Asn	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.1274G>A	p.Ser425Asn	missense_variant	8/8	1	NM_020947.4	ENSP00000343635	P1
MEAK7	ENST00000566995.5 linkuse as main transcript	c.*688G>A		3_prime_UTR_variant, NMD_transcript_variant	9/9	5		ENSP00000454265
MEAK7	ENST00000570036.5 linkuse as main transcript	c.*1329G>A		3_prime_UTR_variant, NMD_transcript_variant	9/9	2		ENSP00000455332

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152252

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000405

AC:

AN:

246610

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133388

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000893

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1451250

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

721142

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74388

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

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

Apr 19, 2024

The c.1274G>A (p.S425N) alteration is located in exon 8 (coding exon 7) of the TLDC1 gene. This alteration results from a G to A substitution at nucleotide position 1274, causing the serine (S) at amino acid position 425 to be replaced by an asparagine (N). 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

Uncertain

0.46

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.80

M_CAP

Benign

0.029

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.3

REVEL

Benign

0.18

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

0.94

Vest4

0.23

MutPred

0.27

Loss of phosphorylation at S425 (P = 0.0387);

MVP

0.29

MPC

0.0055

ClinPred

0.95

GERP RS

4.8

Varity_R

0.44

gMVP

0.73

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