rs8021076

Variant names:

• chr14-77253003-T-C
• rs8021076
• NM_020431.4:c.2149-302T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• spastic paraplegia 87, autosomal recessive

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020431.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM63C	NM_020431.4	MANE Select	c.2149-302T>C		intron	N/A	NP_065164.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM63C	ENST00000298351.5	TSL:1 MANE Select	c.2149-302T>C		intron	N/A	ENSP00000298351.4
	TMEM63C	ENST00000557504.1	TSL:4	n.191-302T>C		intron	N/A

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

African (AFR) AF: 0.123 AC: 5120 AN: 41564

American (AMR) AF: 0.0954 AC: 1461 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 404 AN: 3472

East Asian (EAS) AF: 0.277 AC: 1434 AN: 5170

South Asian (SAS) AF: 0.109 AC: 524 AN: 4824

European-Finnish (FIN) AF: 0.0922 AC: 979 AN: 10616

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7142 AN: 68018

Other (OTH) AF: 0.134 AC: 283 AN: 2112

Alfa AF: 0.109 Hom.: 1712

Bravo AF: 0.116

Asia WGS AF: 0.171 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.44
DANN	Benign	0.71
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8021076; hg19: chr14-77719346; COSMIC: COSV107320246;