Variant 3-171853560-A-T 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_001164436.2(TMEM212):c.253A>T(p.Ile85Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,384,828 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TMEM212
NM_001164436.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.731

Variant links:

Genes affected

TMEM212 (HGNC:34295): (transmembrane protein 212) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM212 links:

TMEM212-AS1 (HGNC:):

TMEM212-AS1 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=0.15570551).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM212	NM_001164436.2 linkuse as main transcript	c.253A>T	p.Ile85Phe	missense_variant	3/5	ENST00000334567.9	NP_001157908.1	A6NML5
TMEM212	XM_011512817.1 linkuse as main transcript	c.253A>T	p.Ile85Phe	missense_variant	3/4		XP_011511119.1	A6NML5
TMEM212	XM_017006376.2 linkuse as main transcript	c.193A>T	p.Ile65Phe	missense_variant	2/3		XP_016861865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM212	ENST00000334567.9 linkuse as main transcript	c.253A>T	p.Ile85Phe	missense_variant	3/5	2	NM_001164436.2	ENSP00000334072.5		A6NML5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000139

AC:

AN:

144102

Hom.:

AF XY:

0.00

AC XY:

AN XY:

76948

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000188

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

AF:

0.00000144

AC:

AN:

1384828

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

683338

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 03, 2023

The c.253A>T (p.I85F) alteration is located in exon 3 (coding exon 3) of the TMEM212 gene. This alteration results from a A to T substitution at nucleotide position 253, causing the isoleucine (I) at amino acid position 85 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

Benign

0.19

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.022

T;T;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.69

.;T;T

M_CAP

Benign

0.084

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.8

L;L;.

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.5

D;.;D

REVEL

Benign

0.061

Sift

Uncertain

0.0090

D;.;D

Sift4G

Uncertain

0.030

D;D;D

Polyphen

0.93

P;P;.

Vest4

0.40

MutPred

0.33

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);.;

MVP

0.41

ClinPred

0.67

GERP RS

0.55

Varity_R

0.29

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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