rs3813539

Variant names:

• chr14-77257883-G-A
• rs3813539
• NM_020431.4:c.*1157G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-77257883-G-A
• chr14-77257883-G-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.*1157G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,298 control chromosomes in the GnomAD database, including 1,171 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 (1170 hom., cov: 33)
  • Exomes 𝑓: 0.087 (1 hom.)
• Consequence: TMEM63C NM_020431.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.900
• Publications: 7 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM63C	NM_020431.4	c.*1157G>A		3_prime_UTR_variant	Exon 24 of 24	ENST00000298351.5	NP_065164.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM63C	ENST00000298351.5	c.*1157G>A		3_prime_UTR_variant	Exon 24 of 24	1	NM_020431.4	ENSP00000298351.4

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16585 AN: 152088 Hom.: 1172 Cov.: 33

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.0888

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.0870 AC: 8 AN: 92 Hom.: 1 Cov.: 0 AF XY: 0.0694 AC XY: 5 AN XY: 72

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.125 AC: 8 AN: 64

Other (OTH) AF: 0.00 AC: 0 AN: 8

GnomAD4 genome AF: 0.109 AC: 16570 AN: 152206 Hom.: 1170 Cov.: 33 AF XY: 0.109 AC XY: 8092 AN XY: 74428

African (AFR) AF: 0.0276 AC: 1145 AN: 41546

American (AMR) AF: 0.123 AC: 1878 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 359 AN: 3472

East Asian (EAS) AF: 0.190 AC: 980 AN: 5170

South Asian (SAS) AF: 0.0889 AC: 429 AN: 4828

European-Finnish (FIN) AF: 0.131 AC: 1386 AN: 10592

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9946 AN: 67986

Other (OTH) AF: 0.123 AC: 260 AN: 2110

Alfa AF: 0.131 Hom.: 2325

Bravo AF: 0.107

Asia WGS AF: 0.128 AC: 443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.2
DANN	Benign	0.43
PhyloP100		0.90
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: rs3813539; hg19: chr14-77724226;