6-37218636-A-C

Variant summary

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

The NM_001286401.2(TMEM217):ā€‹c.395T>Gā€‹(p.Leu132Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 31)

Consequence

TMEM217
NM_001286401.2 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.97
Variant links:
Genes affected
TMEM217 (HGNC:21238): (transmembrane protein 217) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
TMEM217B (HGNC:55922): (transmembrane protein 217B)

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=0.2301473).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMEM217NM_001286401.2 linkc.395T>G p.Leu132Trp missense_variant 2/3 ENST00000651039.2 NP_001273330.1 Q8N7C4-2
TMEM217BNM_001395378.1 linkc.-27-5640T>G intron_variant ENST00000497775.2 NP_001382307.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM217ENST00000651039.2 linkc.395T>G p.Leu132Trp missense_variant 2/3 NM_001286401.2 ENSP00000499204.1 Q8N7C4-2
TMEM217BENST00000497775.2 linkc.-27-5640T>G intron_variant 2 NM_001395378.1 ENSP00000499172.1 A0A494BZU4

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152186
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
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
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152186
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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

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 01, 2022The c.395T>G (p.L132W) alteration is located in exon 2 (coding exon 1) of the TMEM217 gene. This alteration results from a T to G substitution at nucleotide position 395, causing the leucine (L) at amino acid position 132 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
Uncertain
0.44
BayesDel_addAF
Benign
-0.0044
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
17
DANN
Benign
0.90
DEOGEN2
Benign
0.044
.;T
Eigen
Benign
-0.35
Eigen_PC
Benign
-0.41
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.57
T;T
M_CAP
Benign
0.0056
T
MetaRNN
Benign
0.23
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.3
L;L
PrimateAI
Benign
0.42
T
PROVEAN
Uncertain
-2.9
D;D
REVEL
Benign
0.13
Sift
Benign
0.073
T;T
Sift4G
Benign
0.083
T;T
Polyphen
0.75
P;P
Vest4
0.50
MutPred
0.39
Gain of MoRF binding (P = 0.0446);Gain of MoRF binding (P = 0.0446);
MVP
0.17
MPC
0.55
ClinPred
0.35
T
GERP RS
3.3
Varity_R
0.10
gMVP
0.16

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs752128259; hg19: chr6-37186412; API