14-77146567-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000259164	ENST00000557752.1	n.136+40723T>C		intron_variant	Intron 2 of 5	5		ENSP00000456507.1
TMEM63C	ENST00000557408.5	c.-237+29725T>C		intron_variant	Intron 1 of 3	4		ENSP00000450879.1

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

Gnomad4 AFR AF: 0.946

Gnomad4 AMR AF: 0.985

Gnomad4 ASJ AF: 0.954

Gnomad4 EAS AF: 0.899

Gnomad4 SAS AF: 0.976

Gnomad4 FIN AF: 0.990

Gnomad4 NFE AF: 0.983

Gnomad4 OTH AF: 0.970

Alfa AF: 0.978 Hom.: 4298

Bravo AF: 0.966

Asia WGS AF: 0.952 AC: 3311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2020995; hg19: chr14-77612910;