14-77218327-C-G

Variant names:

• chr14-77218327-C-G
• rs4467006
• NM_020431.4:c.-13-474C>G

Variant summary

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

The NM_020431.4(TMEM63C):​c.-13-474C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 151,374 control chromosomes in the GnomAD database, including 35,185 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 0.68 (35185 hom., cov: 29)
• Consequence: TMEM63C NM_020431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920
• Publications: 5 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

ENSG00000259164 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM63C	NM_020431.4	c.-13-474C>G		intron_variant	Intron 2 of 23	ENST00000298351.5	NP_065164.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM63C	ENST00000298351.5	c.-13-474C>G		intron_variant	Intron 2 of 23	1	NM_020431.4	ENSP00000298351.4
ENSG00000259164	ENST00000557752.1	n.137-474C>G		intron_variant	Intron 2 of 5	5		ENSP00000456507.1

Frequencies

GnomAD3 genomes AF: 0.679 AC: 102730 AN: 151254 Hom.: 35179 Cov.: 29

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.708

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.712

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

GnomAD4 genome AF: 0.679 AC: 102781 AN: 151374 Hom.: 35185 Cov.: 29 AF XY: 0.682 AC XY: 50396 AN XY: 73900

African (AFR) AF: 0.589 AC: 24303 AN: 41238

American (AMR) AF: 0.735 AC: 11188 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2471 AN: 3468

East Asian (EAS) AF: 0.647 AC: 3303 AN: 5108

South Asian (SAS) AF: 0.720 AC: 3453 AN: 4794

European-Finnish (FIN) AF: 0.743 AC: 7696 AN: 10356

Middle Eastern (MID) AF: 0.700 AC: 203 AN: 290

European-Non Finnish (NFE) AF: 0.707 AC: 47971 AN: 67878

Other (OTH) AF: 0.710 AC: 1490 AN: 2100

Alfa AF: 0.692 Hom.: 4573

Bravo AF: 0.677

Asia WGS AF: 0.676 AC: 2348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	7.2
DANN	Benign	0.43
PhyloP100		0.092
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: rs4467006; hg19: chr14-77684670;