14-77258661-T-C

Variant names:

• chr14-77258661-T-C
• rs7141596
• NM_020431.4:c.*1935T>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.*1935T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 152,214 control chromosomes in the GnomAD database, including 932 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 0.067 (932 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM63C NM_020431.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 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.*1935T>C		3_prime_UTR	Exon 24 of 24	NP_065164.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM63C	ENST00000298351.5	TSL:1 MANE Select	c.*1935T>C		3_prime_UTR	Exon 24 of 24	ENSP00000298351.4

Frequencies

GnomAD3 genomes AF: 0.0670 AC: 10193 AN: 152096 Hom.: 930 Cov.: 33

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0316

Gnomad FIN AF: 0.0287

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00978

Gnomad OTH AF: 0.0564

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 96 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 76

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 88

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0671 AC: 10219 AN: 152214 Hom.: 932 Cov.: 33 AF XY: 0.0646 AC XY: 4809 AN XY: 74420

African (AFR) AF: 0.207 AC: 8605 AN: 41506

American (AMR) AF: 0.0216 AC: 331 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3468

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5166

South Asian (SAS) AF: 0.0314 AC: 152 AN: 4834

European-Finnish (FIN) AF: 0.0287 AC: 305 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00978 AC: 665 AN: 68006

Other (OTH) AF: 0.0558 AC: 118 AN: 2116

Alfa AF: 0.0271 Hom.: 366

Bravo AF: 0.0724

Asia WGS AF: 0.0310 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.29
PhyloP100		-2.4
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: rs7141596; hg19: chr14-77725004;