3-171843533-T-G

Position:

• chr3-171843533-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001164436.2(TMEM212):​c.150T>G​(p.Asn50Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000725 in 1,379,302 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: 7.3e-7 (0 hom.)
• Consequence: TMEM212 NM_001164436.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.68

Genes affected

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

TMEM212-AS1 (HGNC:):

ACMG classification

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=0.40402627).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM212	NM_001164436.2	c.150T>G	p.Asn50Lys	missense_variant	1/5	ENST00000334567.9	NP_001157908.1
TMEM212	XM_011512817.1	c.150T>G	p.Asn50Lys	missense_variant	1/4		XP_011511119.1
TMEM212	XM_017006376.2	c.150T>G	p.Asn50Lys	missense_variant	1/3		XP_016861865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM212	ENST00000334567.9	c.150T>G	p.Asn50Lys	missense_variant	1/5	2	NM_001164436.2	ENSP00000334072.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.25e-7 AC: 1 AN: 1379302 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 680490

Gnomad4 AFR exome AF: 0.0000319

Gnomad4 AMR exome AF: 0.00

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.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2024

The c.150T>G (p.N50K) alteration is located in exon 1 (coding exon 1) of the TMEM212 gene. This alteration results from a T to G substitution at nucleotide position 150, causing the asparagine (N) at amino acid position 50 to be replaced by a lysine (K). 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	0.74
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T;T;.
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.71	.;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Uncertain	0.21	D
MutationAssessor	Uncertain	2.3	M;M;.
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-5.5	D;.;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0060	D;.;D
Sift4G	Uncertain	0.010	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.73
MutPred		0.40		Gain of ubiquitination at N50 (P = 0.0198);Gain of ubiquitination at N50 (P = 0.0198);.;
MVP		0.52
ClinPred		1.0	D
GERP RS		3.4
Varity_R		0.48
gMVP		0.87

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

Other links and lift over

dbSNP: rs1724761861; hg19: chr3-171561323;