Variant 6-37218636-A-C 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_001286401.2(TMEM217):c.395T>G(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 (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Consequence

TMEM217
NM_001286401.2 missense

Scores

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]

TMEM217 links:

TMEM217B (HGNC:55922): (transmembrane protein 217B)

TMEM217B links:

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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
TMEM217	NM_001286401.2 link	c.395T>G	p.Leu132Trp	missense_variant	2/3	ENST00000651039.2	NP_001273330.1	Q8N7C4-2
TMEM217B	NM_001395378.1 link	c.-27-5640T>G		intron_variant		ENST00000497775.2	NP_001382307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM217	ENST00000651039.2 link	c.395T>G	p.Leu132Trp	missense_variant	2/3		NM_001286401.2	ENSP00000499204.1		Q8N7C4-2
TMEM217B	ENST00000497775.2 link	c.-27-5640T>G		intron_variant		2	NM_001395378.1	ENSP00000499172.1		A0A494BZU4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

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.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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 submitter

clinical testing

Ambry Genetics

Nov 01, 2022

The 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

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.044

.;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;L

PrimateAI

Benign

0.42

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

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.

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