rs8014408

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020431.4(TMEM63C):​c.-14+1222A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 151,108 control chromosomes in the GnomAD database, including 6,258 homozygotes. 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: 𝑓 0.26 ( 6258 hom., cov: 28)

Consequence

TMEM63C
NM_020431.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.874
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMEM63CNM_020431.4 linkuse as main transcriptc.-14+1222A>C intron_variant ENST00000298351.5 NP_065164.2 Q9P1W3A0A024R6B3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM63CENST00000298351.5 linkuse as main transcriptc.-14+1222A>C intron_variant 1 NM_020431.4 ENSP00000298351.4 Q9P1W3
ENSG00000259164ENST00000557752.1 linkuse as main transcriptn.137-4071A>C intron_variant 5 ENSP00000456507.1 H3BS24

Frequencies

GnomAD3 genomes
AF:
0.257
AC:
38742
AN:
150986
Hom.:
6253
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.0833
Gnomad AMI
AF:
0.330
Gnomad AMR
AF:
0.228
Gnomad ASJ
AF:
0.277
Gnomad EAS
AF:
0.613
Gnomad SAS
AF:
0.494
Gnomad FIN
AF:
0.277
Gnomad MID
AF:
0.306
Gnomad NFE
AF:
0.319
Gnomad OTH
AF:
0.262
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.256
AC:
38745
AN:
151108
Hom.:
6258
Cov.:
28
AF XY:
0.260
AC XY:
19152
AN XY:
73750
show subpopulations
Gnomad4 AFR
AF:
0.0832
Gnomad4 AMR
AF:
0.228
Gnomad4 ASJ
AF:
0.277
Gnomad4 EAS
AF:
0.613
Gnomad4 SAS
AF:
0.495
Gnomad4 FIN
AF:
0.277
Gnomad4 NFE
AF:
0.319
Gnomad4 OTH
AF:
0.261
Alfa
AF:
0.274
Hom.:
2501
Bravo
AF:
0.244
Asia WGS
AF:
0.501
AC:
1742
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
8.3
DANN
Benign
0.81

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.

Other links and lift over

dbSNP: rs8014408; hg19: chr14-77681073; API