chr14-77162674-A-T

Position:

• chr14-77162674-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000557752.1(ENSG00000259164):​n.137-56127A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,100 control chromosomes in the GnomAD database, including 8,178 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 0.30 (8178 hom., cov: 31)
• Consequence: ENSG00000259164 ENST00000557752.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.77162674A>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000259164	ENST00000557752.1	n.137-56127A>T		intron_variant		5		ENSP00000456507.1
TMEM63C	ENST00000557408.5	c.-236-33397A>T		intron_variant		4		ENSP00000450879.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45465 AN: 151982 Hom.: 8184 Cov.: 31

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.299 AC: 45442 AN: 152100 Hom.: 8178 Cov.: 31 AF XY: 0.303 AC XY: 22497 AN XY: 74360

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.523

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.298

Alfa AF: 0.202 Hom.: 498

Bravo AF: 0.281

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.38
DANN	Benign	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

Publications

LitVar

Other links and lift over

dbSNP: rs981471; hg19: chr14-77629017;