6-37218973-C-A

Variant summary

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

The NM_001286401.2(TMEM217):​c.58G>T​(p.Val20Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,614,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

TMEM217
NM_001286401.2 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.435
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=0.156059).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM217NM_001286401.2 linkc.58G>T p.Val20Phe missense_variant Exon 2 of 3 ENST00000651039.2 NP_001273330.1 Q8N7C4-2
TMEM217BNM_001395378.1 linkc.-27-5977G>T intron_variant Intron 1 of 1 ENST00000497775.2 NP_001382307.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM217ENST00000651039.2 linkc.58G>T p.Val20Phe missense_variant Exon 2 of 3 NM_001286401.2 ENSP00000499204.1 Q8N7C4-2
TMEM217BENST00000497775.2 linkc.-27-5977G>T intron_variant Intron 1 of 1 2 NM_001395378.1 ENSP00000499172.1 A0A494BZU4

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152154
Hom.:
0
Cov.:
31
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:
0.000191
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000836
AC:
21
AN:
251164
Hom.:
0
AF XY:
0.0000589
AC XY:
8
AN XY:
135814
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000150
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000116
AC:
169
AN:
1461888
Hom.:
0
Cov.:
31
AF XY:
0.000103
AC XY:
75
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000562
Gnomad4 NFE exome
AF:
0.000141
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152272
Hom.:
0
Cov.:
31
AF XY:
0.0000940
AC XY:
7
AN XY:
74444
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:
0.000191
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000104
Hom.:
0
Bravo
AF:
0.0000793
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000906
AC:
11
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 28, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.58G>T (p.V20F) alteration is located in exon 2 (coding exon 1) of the TMEM217 gene. This alteration results from a G to T substitution at nucleotide position 58, causing the valine (V) at amino acid position 20 to be replaced by a phenylalanine (F). 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
0.36
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.14
.;T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.080
N
LIST_S2
Benign
0.65
T;T
M_CAP
Benign
0.0081
T
MetaRNN
Benign
0.16
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
L;L
PrimateAI
Benign
0.40
T
PROVEAN
Uncertain
-3.6
D;D
REVEL
Benign
0.088
Sift
Uncertain
0.0090
D;D
Sift4G
Uncertain
0.0060
D;D
Polyphen
0.18
B;P
Vest4
0.44
MVP
0.081
MPC
1.0
ClinPred
0.13
T
GERP RS
3.9
Varity_R
0.34
gMVP
0.69

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: rs200392924; hg19: chr6-37186749; COSMIC: COSV60827033; COSMIC: COSV60827033; API