Variant chr14-77218829-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020431.4(TMEM63C):c.16G>C(p.Asp6His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

TMEM63C
NM_020431.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.913

Variant links:

Genes affected

TMEM63C (HGNC:23787): (transmembrane protein 63C) Enables calcium activated cation channel activity. Involved in cation transport. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. Biomarker of focal segmental glomerulosclerosis. [provided by Alliance of Genome Resources, Apr 2022]

TMEM63C 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=0.10490501).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM63C	NM_020431.4 linkuse as main transcript	c.16G>C	p.Asp6His	missense_variant	3/24	ENST00000298351.5	NP_065164.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM63C	ENST00000298351.5 linkuse as main transcript	c.16G>C	p.Asp6His	missense_variant	3/24	1	NM_020431.4	ENSP00000298351	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461134

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726828

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:

0.00000360

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

May 17, 2023

The c.16G>C (p.D6H) alteration is located in exon 3 (coding exon 1) of the TMEM63C gene. This alteration results from a G to C substitution at nucleotide position 16, causing the aspartic acid (D) at amino acid position 6 to be replaced by a histidine (H). 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

0.081

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.7

DANN

Benign

0.66

DEOGEN2

Benign

0.012

.;.;.;T;.;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.37

T;T;T;T;T;T

M_CAP

Benign

0.0071

MetaRNN

Benign

0.10

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

.;.;.;.;.;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Pathogenic

-5.3

D;D;D;N;D;N

REVEL

Benign

0.078

Sift

Benign

0.044

.;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;T;T;D;D;D

Polyphen

0.94

.;.;.;.;.;P

Vest4

0.18

MutPred

0.16

Gain of catalytic residue at T10 (P = 0.0172);Gain of catalytic residue at T10 (P = 0.0172);Gain of catalytic residue at T10 (P = 0.0172);Gain of catalytic residue at T10 (P = 0.0172);Gain of catalytic residue at T10 (P = 0.0172);Gain of catalytic residue at T10 (P = 0.0172);

MVP

0.082

MPC

0.81

ClinPred

0.75

GERP RS

1.0

Varity_R

0.046

gMVP

0.49

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