Variant 3-171853650-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001164436.2(TMEM212):c.343A>T(p.Thr115Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000866 in 1,385,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000087 ( 0 hom. )

Consequence

TMEM212
NM_001164436.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.55

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:41939): (TMEM212 antisense RNA 1)

TMEM212-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.331431).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM212	NM_001164436.2 link	c.343A>T	p.Thr115Ser	missense_variant	3/5	ENST00000334567.9	NP_001157908.1	A6NML5
TMEM212	XM_011512817.1 link	c.343A>T	p.Thr115Ser	missense_variant	3/4		XP_011511119.1	A6NML5
TMEM212	XM_017006376.2 link	c.283A>T	p.Thr95Ser	missense_variant	2/3		XP_016861865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM212	ENST00000334567.9 link	c.343A>T	p.Thr115Ser	missense_variant	3/5	2	NM_001164436.2	ENSP00000334072.5		A6NML5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000205

AC:

AN:

146052

Hom.:

AF XY:

0.0000258

AC XY:

AN XY:

77552

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000282

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:

0.00000866

AC:

AN:

1385204

Hom.:

Cov.:

AF XY:

0.00000585

AC XY:

AN XY:

683512

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000336

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.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Mar 22, 2023

The c.343A>T (p.T115S) 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 343, causing the threonine (T) at amino acid position 115 to be replaced by a serine (S). 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

0.20

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.041

T;T;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.60

.;T;T

M_CAP

Benign

0.048

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Uncertain

-0.14

MutationAssessor

Uncertain

2.3

M;M;.

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.7

D;.;D

REVEL

Benign

0.29

Sift

Uncertain

0.021

D;.;D

Sift4G

Uncertain

0.041

D;D;D

Polyphen

0.97

D;D;.

Vest4

0.34

MutPred

0.26

Loss of glycosylation at S110 (P = 0.0203);Loss of glycosylation at S110 (P = 0.0203);.;

MVP

0.49

ClinPred

0.86

GERP RS

4.8

Varity_R

0.26

gMVP

0.45

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.

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