rs17750404

Positions:

• chr14-77233590-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.542+90C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,374,606 control chromosomes in the GnomAD database, including 46,924 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 0.22 (4382 hom., cov: 30)
  • Exomes 𝑓: 0.26 (42542 hom.)
• Consequence: TMEM63C NM_020431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM63C	NM_020431.4	c.542+90C>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.542+90C>T		intron_variant		1	NM_020431.4	ENSP00000298351.4

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33293 AN: 151506 Hom.: 4372 Cov.: 30

Gnomad AFR AF: 0.0854

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.246

GnomAD4 exome AF: 0.258 AC: 315199 AN: 1222980 Hom.: 42542 AF XY: 0.255 AC XY: 155934 AN XY: 612602

Gnomad4 AFR exome AF: 0.0796

Gnomad4 AMR exome AF: 0.312

Gnomad4 ASJ exome AF: 0.238

Gnomad4 EAS exome AF: 0.159

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.273

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.220 AC: 33326 AN: 151626 Hom.: 4382 Cov.: 30 AF XY: 0.222 AC XY: 16457 AN XY: 74036

Gnomad4 AFR AF: 0.0855

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.246

Alfa AF: 0.262 Hom.: 7174

Bravo AF: 0.216

Asia WGS AF: 0.172 AC: 595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.2
DANN	Benign	0.51

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: rs17750404; hg19: chr14-77699933; COSMIC: COSV53603710; COSMIC: COSV53603710;