chr14-77257883-G-A

Position:

• chr14-77257883-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000298351.5(TMEM63C):​c.*1157G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,298 control chromosomes in the GnomAD database, including 1,171 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 0.11 (1170 hom., cov: 33)
  • Exomes 𝑓: 0.087 (1 hom.)
• Consequence: TMEM63C ENST00000298351.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.900

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM63C	NM_020431.4	c.*1157G>A		3_prime_UTR_variant	24/24	ENST00000298351.5	NP_065164.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM63C	ENST00000298351.5	c.*1157G>A		3_prime_UTR_variant	24/24	1	NM_020431.4	ENSP00000298351	P1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16585 AN: 152088 Hom.: 1172 Cov.: 33

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.0888

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.0870 AC: 8 AN: 92 Hom.: 1 Cov.: 0 AF XY: 0.0694 AC XY: 5 AN XY: 72

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 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.109 AC: 16570 AN: 152206 Hom.: 1170 Cov.: 33 AF XY: 0.109 AC XY: 8092 AN XY: 74428

Gnomad4 AFR AF: 0.0276

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.0889

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.123

Alfa AF: 0.130 Hom.: 1599

Bravo AF: 0.107

Asia WGS AF: 0.128 AC: 443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.2
DANN	Benign	0.43

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

Other links and lift over

dbSNP: rs3813539; hg19: chr14-77724226;