Variant 3-171853718-C-A 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.411C>A(p.Asp137Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,385,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

TMEM212
NM_001164436.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.103

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34626204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM212	NM_001164436.2 linkuse as main transcript	c.411C>A	p.Asp137Glu	missense_variant	3/5	ENST00000334567.9	NP_001157908.1	A6NML5
TMEM212	XM_011512817.1 linkuse as main transcript	c.411C>A	p.Asp137Glu	missense_variant	3/4		XP_011511119.1	A6NML5
TMEM212	XM_017006376.2 linkuse as main transcript	c.351C>A	p.Asp117Glu	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.411C>A	p.Asp137Glu	missense_variant	3/5	2	NM_001164436.2	ENSP00000334072.5		A6NML5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000685

AC:

AN:

146050

Hom.:

AF XY:

0.00

AC XY:

AN XY:

77534

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000406

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.22e-7

AC:

AN:

1385220

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

683506

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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

Dec 04, 2024

The c.411C>A (p.D137E) alteration is located in exon 3 (coding exon 3) of the TMEM212 gene. This alteration results from a C to A substitution at nucleotide position 411, causing the aspartic acid (D) at amino acid position 137 to be replaced by a glutamic acid (E). 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

Pathogenic

0.57

BayesDel_addAF

Benign

-0.023

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.083

T;T;.

Eigen

Benign

0.063

Eigen_PC

Benign

0.0037

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.64

.;T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Uncertain

-0.27

MutationAssessor

Uncertain

2.4

M;M;.

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-4.0

D;.;D

REVEL

Uncertain

0.38

Sift

Pathogenic

0.0

D;.;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.98

D;D;.

Vest4

0.71

MutPred

0.41

Gain of disorder (P = 0.1245);Gain of disorder (P = 0.1245);.;

MVP

0.29

ClinPred

0.99

GERP RS

2.8

Varity_R

0.64

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