chr9-68537399-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153237.2(TMEM252):ā€‹c.373C>Gā€‹(p.Leu125Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 152,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 33)

Consequence

TMEM252
NM_153237.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23
Variant links:
Genes affected
TMEM252 (HGNC:28537): (transmembrane protein 252) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04546371).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TMEM252NM_153237.2 linkuse as main transcriptc.373C>G p.Leu125Val missense_variant 2/2 ENST00000377311.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TMEM252ENST00000377311.4 linkuse as main transcriptc.373C>G p.Leu125Val missense_variant 2/21 NM_153237.2 P1

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152220
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000408
AC:
1
AN:
245082
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
132698
show subpopulations
Gnomad AFR exome
AF:
0.0000625
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152220
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.000121
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

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 submitterclinical testingAmbry GeneticsNov 21, 2022The c.373C>G (p.L125V) alteration is located in exon 2 (coding exon 2) of the TMEM252 gene. This alteration results from a C to G substitution at nucleotide position 373, causing the leucine (L) at amino acid position 125 to be replaced by a valine (V). 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
0.081
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
7.4
DANN
Benign
0.95
DEOGEN2
Benign
0.032
T
Eigen
Benign
-0.74
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.55
T
M_CAP
Benign
0.0019
T
MetaRNN
Benign
0.045
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
2.0
M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-2.2
N
REVEL
Benign
0.097
Sift
Benign
0.15
T
Sift4G
Benign
0.24
T
Polyphen
0.015
B
Vest4
0.038
MutPred
0.14
Loss of catalytic residue at L125 (P = 0.0573);
MVP
0.030
MPC
0.051
ClinPred
0.031
T
GERP RS
2.5
Varity_R
0.14
gMVP
0.18

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.

Other links and lift over

dbSNP: rs1028117078; hg19: chr9-71152315; COSMIC: COSV101051069; COSMIC: COSV101051069; API