chr16-84482598-G-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_020947.4(MEAK7):āc.1071C>Gā(p.Asn357Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 34)
Exomes š: 0.000014 ( 0 hom. )
Consequence
MEAK7
NM_020947.4 missense
NM_020947.4 missense
Scores
6
4
9
Clinical Significance
Conservation
PhyloP100: -0.786
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.867
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEAK7 | NM_020947.4 | c.1071C>G | p.Asn357Lys | missense_variant | 6/8 | ENST00000343629.11 | |
MEAK7 | XM_005256075.3 | c.1071C>G | p.Asn357Lys | missense_variant | 7/9 | ||
MEAK7 | XM_017023511.2 | c.1071C>G | p.Asn357Lys | missense_variant | 6/8 | ||
MEAK7 | XM_047434410.1 | c.1071C>G | p.Asn357Lys | missense_variant | 6/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEAK7 | ENST00000343629.11 | c.1071C>G | p.Asn357Lys | missense_variant | 6/8 | 1 | NM_020947.4 | P1 | |
MEAK7 | ENST00000566995.5 | c.*485C>G | 3_prime_UTR_variant, NMD_transcript_variant | 7/9 | 5 | ||||
MEAK7 | ENST00000570036.5 | c.*1126C>G | 3_prime_UTR_variant, NMD_transcript_variant | 7/9 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152242Hom.: 0 Cov.: 34
GnomAD3 genomes
AF:
AC:
4
AN:
152242
Hom.:
Cov.:
34
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461826Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727212
GnomAD4 exome
AF:
AC:
21
AN:
1461826
Hom.:
Cov.:
31
AF XY:
AC XY:
9
AN XY:
727212
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152242Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3AN XY: 74380
GnomAD4 genome
AF:
AC:
4
AN:
152242
Hom.:
Cov.:
34
AF XY:
AC XY:
3
AN XY:
74380
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
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 13, 2021 | The c.1071C>G (p.N357K) alteration is located in exon 6 (coding exon 5) of the TLDC1 gene. This alteration results from a C to G substitution at nucleotide position 1071, causing the asparagine (N) at amino acid position 357 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of glycosylation at N357 (P = 0.0076);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at