14-77255805-C-T

Position:

• chr14-77255805-C-T

Variant summary

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

The NM_020431.4(TMEM63C):​c.2221-721C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 152,138 control chromosomes in the GnomAD database, including 15,909 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 0.42 (15909 hom., cov: 33)
• Consequence: TMEM63C NM_020431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM63C	NM_020431.4	c.2221-721C>T		intron_variant		ENST00000298351.5	NP_065164.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM63C	ENST00000298351.5	c.2221-721C>T		intron_variant		1	NM_020431.4	ENSP00000298351.4
TMEM63C	ENST00000557504.1	n.263-721C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64261 AN: 152020 Hom.: 15851 Cov.: 33

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.418

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.423 AC: 64379 AN: 152138 Hom.: 15909 Cov.: 33 AF XY: 0.425 AC XY: 31632 AN XY: 74376

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.424

Alfa AF: 0.393 Hom.: 2557

Bravo AF: 0.449

Asia WGS AF: 0.512 AC: 1782 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	1.0
DANN	Benign	0.35

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: rs888059; hg19: chr14-77722148;