14-77258661-T-C

Position:

• chr14-77258661-T-C

Variant summary

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

The NM_020431.4(TMEM63C):​c.*1935T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 152,214 control chromosomes in the GnomAD database, including 932 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 0.067 (932 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM63C NM_020431.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM63C	NM_020431.4	c.*1935T>C		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.*1935T>C		3_prime_UTR_variant	24/24	1	NM_020431.4	ENSP00000298351.4

Frequencies

GnomAD3 genomes AF: 0.0670 AC: 10193 AN: 152096 Hom.: 930 Cov.: 33

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0316

Gnomad FIN AF: 0.0287

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00978

Gnomad OTH AF: 0.0564

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 96 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 76

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 AF: 0.0671 AC: 10219 AN: 152214 Hom.: 932 Cov.: 33 AF XY: 0.0646 AC XY: 4809 AN XY: 74420

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.0216

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.0314

Gnomad4 FIN AF: 0.0287

Gnomad4 NFE AF: 0.00978

Gnomad4 OTH AF: 0.0558

Alfa AF: 0.0183 Hom.: 148

Bravo AF: 0.0724

Asia WGS AF: 0.0310 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.29

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: rs7141596; hg19: chr14-77725004;