14-77146567-T-C

Variant names:

• chr14-77146567-T-C
• rs2020995
• ENST00000557752.1:n.136+40723T>C

Variant summary

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

The ENST00000557752.1(ENSG00000259164):​n.136+40723T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.97 in 152,098 control chromosomes in the GnomAD database, including 71,551 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 0.97 (71551 hom., cov: 28)
• Consequence: ENSG00000259164 ENST00000557752.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.849
• Publications: 1 publications found

Genes affected

ENSG00000259164 (HGNC:):

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: STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000557752.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000259164	ENST00000557752.1	TSL:5	n.136+40723T>C		intron	N/A	ENSP00000456507.1	H3BS24
	TMEM63C	ENST00000557408.5	TSL:4	c.-237+29725T>C		intron	N/A	ENSP00000450879.1	G3V2V1

Frequencies

GnomAD3 genomes AF: 0.970 AC: 147357 AN: 151980 Hom.: 71495 Cov.: 28

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.985

Gnomad ASJ AF: 0.954

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.976

Gnomad FIN AF: 0.990

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.983

Gnomad OTH AF: 0.969

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

GnomAD4 genome AF: 0.970 AC: 147472 AN: 152098 Hom.: 71551 Cov.: 28 AF XY: 0.970 AC XY: 72070 AN XY: 74316

African (AFR) AF: 0.946 AC: 39235 AN: 41472

American (AMR) AF: 0.985 AC: 15065 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.954 AC: 3310 AN: 3470

East Asian (EAS) AF: 0.899 AC: 4611 AN: 5130

South Asian (SAS) AF: 0.976 AC: 4690 AN: 4806

European-Finnish (FIN) AF: 0.990 AC: 10489 AN: 10598

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.983 AC: 66849 AN: 68014

Other (OTH) AF: 0.970 AC: 2046 AN: 2110

Alfa AF: 0.974 Hom.: 99469

Bravo AF: 0.966

Asia WGS AF: 0.952 AC: 3311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.86
DANN	Benign	0.63
PhyloP100		-0.85

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: rs2020995; hg19: chr14-77612910;