Genetic Variant NM_178545.4:c.106G>T (chr1-1919067-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178545.4(TMEM52):c.106G>T(p.Gly36Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000299 in 1,339,580 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: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 8.4e-7 ( 0 hom. )

Consequence

TMEM52
NM_178545.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.894

Variant links:

Genes affected

TMEM52 (HGNC:27916): (transmembrane protein 52) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM52 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13322046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM52	NM_178545.4 link	c.106G>T	p.Gly36Cys	missense_variant	Exon 2 of 5	ENST00000310991.8	NP_848640.1	Q8NDY8-1
TMEM52	XM_047419236.1 link	c.199G>T	p.Gly67Cys	missense_variant	Exon 1 of 4		XP_047275192.1
TMEM52	XM_047419237.1 link	c.199G>T	p.Gly67Cys	missense_variant	Exon 1 of 3		XP_047275193.1
TMEM52	XM_047419240.1 link	c.106G>T	p.Gly36Cys	missense_variant	Exon 2 of 4		XP_047275196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM52	ENST00000310991.8 link	c.106G>T	p.Gly36Cys	missense_variant	Exon 2 of 5	1	NM_178545.4	ENSP00000311122.3		Q8NDY8-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

8.42e-7

AC:

AN:

1187470

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

571344

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000102

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000304

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 21, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.106G>T (p.G36C) alteration is located in exon 2 (coding exon 2) of the TMEM52 gene. This alteration results from a G to T substitution at nucleotide position 106, causing the glycine (G) at amino acid position 36 to be replaced by a cysteine (C). 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

0.18

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0037

T;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.48

T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.5

N;D

REVEL

Benign

0.063

Sift

Benign

0.041

D;D

Sift4G

Uncertain

0.043

D;D

Polyphen

1.0

D;.

Vest4

0.20

MutPred

0.32

Loss of disorder (P = 0.0309);.;

MVP

0.076

MPC

3.2

ClinPred

0.76

GERP RS

-4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.16

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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