Variant chr2-39666294-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_152390.3(TMEM178A):c.320T>C(p.Leu107Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L107V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TMEM178A
NM_152390.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.325

Variant links:

Genes affected

TMEM178A (HGNC:28517): (transmembrane protein 178A) Predicted to be involved in negative regulation of osteoclast differentiation and regulation of cytosolic calcium ion concentration. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM178A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.805

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM178A	NM_152390.3 linkuse as main transcript	c.320T>C	p.Leu107Pro	missense_variant	1/4	ENST00000281961.3	NP_689603.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM178A	ENST00000281961.3 linkuse as main transcript	c.320T>C	p.Leu107Pro	missense_variant	1/4	1	NM_152390.3	ENSP00000281961	P1	Q8NBL3-1
TMEM178A	ENST00000437068.5 linkuse as main transcript	n.367+946T>C		intron_variant, non_coding_transcript_variant		4
TMEM178A	ENST00000482239.5 linkuse as main transcript	n.143+654T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1275638

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

630134

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:

0.00

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

Jul 26, 2022

The c.320T>C (p.L107P) alteration is located in exon 1 (coding exon 1) of the TMEM178A gene. This alteration results from a T to C substitution at nucleotide position 320, causing the leucine (L) at amino acid position 107 to be replaced by a proline (P). 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

0.90

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.092

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.72

M_CAP

Pathogenic

0.96

MetaRNN

Pathogenic

0.81

MetaSVM

Benign

-0.33

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.57

Sift

Benign

0.056

Sift4G

Benign

0.072

Polyphen

1.0

Vest4

0.78

MutPred

0.56

Loss of helix (P = 0.028);

MVP

0.55

MPC

2.3

ClinPred

0.83

GERP RS

3.5

Varity_R

0.33

gMVP

0.90

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over