chr14-77256124-C-T

Variant names:

• chr14-77256124-C-T
• rs733416
• NM_020431.4:c.2221-402C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020431.4(TMEM63C):​c.2221-402C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,138 control chromosomes in the GnomAD database, including 4,334 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 (4334 hom., cov: 32)
• Consequence: TMEM63C NM_020431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.587 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM63C	NM_020431.4	MANE Select	c.2221-402C>T		intron	N/A	NP_065164.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM63C	ENST00000298351.5	TSL:1 MANE Select	c.2221-402C>T		intron	N/A	ENSP00000298351.4
	TMEM63C	ENST00000890516.1		c.2221-399C>T		intron	N/A	ENSP00000560575.1
	TMEM63C	ENST00000890513.1		c.2221-402C>T		intron	N/A	ENSP00000560572.1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33478 AN: 152020 Hom.: 4328 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.220 AC: 33495 AN: 152138 Hom.: 4334 Cov.: 32 AF XY: 0.226 AC XY: 16773 AN XY: 74356

African (AFR) AF: 0.159 AC: 6588 AN: 41504

American (AMR) AF: 0.332 AC: 5065 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 952 AN: 3470

East Asian (EAS) AF: 0.605 AC: 3124 AN: 5164

South Asian (SAS) AF: 0.289 AC: 1394 AN: 4820

European-Finnish (FIN) AF: 0.171 AC: 1814 AN: 10602

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13742 AN: 67992

Other (OTH) AF: 0.245 AC: 517 AN: 2110

Alfa AF: 0.217 Hom.: 12251

Bravo AF: 0.231

Asia WGS AF: 0.375 AC: 1305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.58
PhyloP100		-0.68
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: rs733416; hg19: chr14-77722467;