14-77218499-A-T

Variant names:

• chr14-77218499-A-T
• rs2287375
• NM_020431.4:c.-13-302A>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.-13-302A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 152,180 control chromosomes in the GnomAD database, including 37,122 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 0.70 (37122 hom., cov: 33)
• Consequence: TMEM63C NM_020431.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.959
• 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

ENSG00000259164 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM63C	NM_020431.4	c.-13-302A>T		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.-13-302A>T		intron_variant	Intron 2 of 23	1	NM_020431.4	ENSP00000298351.4
ENSG00000259164	ENST00000557752.1	n.137-302A>T		intron_variant	Intron 2 of 5	5		ENSP00000456507.1

Frequencies

GnomAD3 genomes AF: 0.697 AC: 106043 AN: 152062 Hom.: 37104 Cov.: 33

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.697 AC: 106114 AN: 152180 Hom.: 37122 Cov.: 33 AF XY: 0.700 AC XY: 52049 AN XY: 74402

African (AFR) AF: 0.653 AC: 27103 AN: 41506

American (AMR) AF: 0.741 AC: 11337 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2473 AN: 3472

East Asian (EAS) AF: 0.644 AC: 3327 AN: 5168

South Asian (SAS) AF: 0.721 AC: 3484 AN: 4832

European-Finnish (FIN) AF: 0.745 AC: 7890 AN: 10590

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48064 AN: 67996

Other (OTH) AF: 0.722 AC: 1526 AN: 2114

Alfa AF: 0.615 Hom.: 1811

Bravo AF: 0.697

Asia WGS AF: 0.680 AC: 2360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.067
DANN	Benign	0.29
PhyloP100		-0.96
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: rs2287375; hg19: chr14-77684842;