Variant 3-171843411-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001164436.2(TMEM212):c.28C>T(p.Arg10Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000312 in 1,536,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

TMEM212
NM_001164436.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.46

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052410007).

BP6

Variant 3-171843411-C-T is Benign according to our data. Variant chr3-171843411-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2391024.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM212	NM_001164436.2 linkuse as main transcript	c.28C>T	p.Arg10Trp	missense_variant	1/5	ENST00000334567.9	NP_001157908.1	A6NML5
TMEM212	XM_011512817.1 linkuse as main transcript	c.28C>T	p.Arg10Trp	missense_variant	1/4		XP_011511119.1	A6NML5
TMEM212	XM_017006376.2 linkuse as main transcript	c.28C>T	p.Arg10Trp	missense_variant	1/3		XP_016861865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM212	ENST00000334567.9 linkuse as main transcript	c.28C>T	p.Arg10Trp	missense_variant	1/5	2	NM_001164436.2	ENSP00000334072.5	A6NML5
TMEM212	ENST00000619900.4 linkuse as main transcript	c.28C>T	p.Arg10Trp	missense_variant	1/4	3		ENSP00000484106.1	A6NML5
TMEM212	ENST00000420375.5 linkuse as main transcript	n.10C>T		non_coding_transcript_exon_variant	1/7	5		ENSP00000410327.1	H7C390
TMEM212-AS1	ENST00000449106.2 linkuse as main transcript	n.526-27483G>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000139

AC:

AN:

144084

Hom.:

AF XY:

0.0000130

AC XY:

AN XY:

76884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000338

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000311

AC:

AN:

1384130

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

682984

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000352

Gnomad4 OTH exome

AF:

0.0000691

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 22, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.16

CADD

Benign

0.034

DANN

Benign

0.71

DEOGEN2

Benign

0.029

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.59

.;T

M_CAP

Benign

0.058

MetaRNN

Benign

0.052

T;T

MetaSVM

Benign

-0.33

MutationAssessor

Benign

1.3

L;L

PrimateAI

Benign

0.18

PROVEAN

Benign

-0.49

N;.

REVEL

Uncertain

0.48

Sift

Benign

0.070

T;.

Sift4G

Uncertain

0.057

T;T

Polyphen

0.0030

B;B

Vest4

0.094

MutPred

0.46

Loss of disorder (P = 0.0349);Loss of disorder (P = 0.0349);

MVP

0.30

ClinPred

0.062

GERP RS

-7.6

Varity_R

0.039

gMVP

0.67

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