rs8021076

Positions:

• chr14-77253003-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.2149-302T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,290 control chromosomes in the GnomAD database, including 1,156 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 (1156 hom., cov: 33)
• Consequence: TMEM63C NM_020431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM63C	NM_020431.4	c.2149-302T>C		intron_variant		ENST00000298351.5	NP_065164.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM63C	ENST00000298351.5	c.2149-302T>C		intron_variant		1	NM_020431.4	ENSP00000298351	P1
TMEM63C	ENST00000557504.1	n.191-302T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17416 AN: 152172 Hom.: 1150 Cov.: 33

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0956

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0922

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.115 AC: 17442 AN: 152290 Hom.: 1156 Cov.: 33 AF XY: 0.116 AC XY: 8668 AN XY: 74452

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.0954

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0922

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.134

Alfa AF: 0.108 Hom.: 1196

Bravo AF: 0.116

Asia WGS AF: 0.171 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.44
DANN	Benign	0.71

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: rs8021076; hg19: chr14-77719346;