14-77257629-G-T

Position:

• chr14-77257629-G-T

Variant summary

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

The NM_020431.4(TMEM63C):​c.*903G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,156 control chromosomes in the GnomAD database, including 4,313 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 0.21 (4313 hom., cov: 32)
  • Exomes 𝑓: 0.15 (0 hom.)
• Consequence: TMEM63C NM_020431.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM63C	NM_020431.4	c.*903G>T		3_prime_UTR_variant	24/24	ENST00000298351.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM63C	ENST00000298351.5	c.*903G>T		3_prime_UTR_variant	24/24	1	NM_020431.4	P1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32223 AN: 151990 Hom.: 4310 Cov.: 32

Gnomad AFR AF: 0.0659

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0438

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.146 AC: 7 AN: 48 Hom.: 0 Cov.: 0 AF XY: 0.0667 AC XY: 2 AN XY: 30

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.212 AC: 32228 AN: 152108 Hom.: 4313 Cov.: 32 AF XY: 0.213 AC XY: 15833 AN XY: 74376

Gnomad4 AFR AF: 0.0657

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.0439

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.208

Alfa AF: 0.248 Hom.: 5308

Bravo AF: 0.195

Asia WGS AF: 0.154 AC: 532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.5
DANN	Benign	0.80

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: rs11847091; hg19: chr14-77723972;