Variant 3-171843412-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001164436.2(TMEM212):c.29G>A(p.Arg10Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000586 in 1,536,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

TMEM212
NM_001164436.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.794

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.032663673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM212	NM_001164436.2 linkuse as main transcript	c.29G>A	p.Arg10Gln	missense_variant	1/5	ENST00000334567.9	NP_001157908.1	A6NML5
TMEM212	XM_011512817.1 linkuse as main transcript	c.29G>A	p.Arg10Gln	missense_variant	1/4		XP_011511119.1	A6NML5
TMEM212	XM_017006376.2 linkuse as main transcript	c.29G>A	p.Arg10Gln	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.29G>A	p.Arg10Gln	missense_variant	1/5	2	NM_001164436.2	ENSP00000334072.5	A6NML5
TMEM212	ENST00000619900.4 linkuse as main transcript	c.29G>A	p.Arg10Gln	missense_variant	1/4	3		ENSP00000484106.1	A6NML5
TMEM212	ENST00000420375.5 linkuse as main transcript	n.11G>A		non_coding_transcript_exon_variant	1/7	5		ENSP00000410327.1	H7C390
TMEM212-AS1	ENST00000449106.2 linkuse as main transcript	n.526-27484C>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000139

AC:

AN:

144046

Hom.:

AF XY:

0.000143

AC XY:

AN XY:

76850

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.000573

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000144

Gnomad NFE exome

AF:

0.0000338

Gnomad OTH exome

AF:

0.000469

GnomAD4 exome

AF:

0.0000585

AC:

AN:

1383998

Hom.:

Cov.:

AF XY:

0.0000571

AC XY:

AN XY:

682914

show subpopulations

Gnomad4 AFR exome

AF:

0.0000951

Gnomad4 AMR exome

AF:

0.000477

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000224

Gnomad4 SAS exome

AF:

0.0000253

Gnomad4 FIN exome

AF:

0.000343

Gnomad4 NFE exome

AF:

0.0000223

Gnomad4 OTH exome

AF:

0.000242

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000567

Asia WGS

AF:

0.000866

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

Dec 19, 2023

The c.29G>A (p.R10Q) alteration is located in exon 1 (coding exon 1) of the TMEM212 gene. This alteration results from a G to A substitution at nucleotide position 29, causing the arginine (R) at amino acid position 10 to be replaced by a glutamine (Q). 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

0.088

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.17

CADD

Benign

8.9

DANN

Benign

0.90

DEOGEN2

Benign

0.031

T;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.55

.;T

M_CAP

Benign

0.083

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-0.33

MutationAssessor

Benign

0.85

L;L

PrimateAI

Benign

0.18

PROVEAN

Benign

-0.62

N;.

REVEL

Benign

0.26

Sift

Benign

0.37

T;.

Sift4G

Benign

0.39

T;T

Polyphen

0.028

B;B

Vest4

0.039

MutPred

0.38

Loss of MoRF binding (P = 0.0414);Loss of MoRF binding (P = 0.0414);

MVP

0.12

ClinPred

0.019

GERP RS

0.81

Varity_R

0.044

gMVP

0.46

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