14-77162674-A-T

Variant names:

• chr14-77162674-A-T
• rs981471
• ENST00000557752.1:n.137-56127A>T

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.634 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.137-56127A>T		intron	N/A	ENSP00000456507.1	H3BS24
	TMEM63C	ENST00000557408.5	TSL:4	c.-236-33397A>T		intron	N/A	ENSP00000450879.1	G3V2V1

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

African (AFR) AF: 0.120 AC: 4998 AN: 41520

American (AMR) AF: 0.250 AC: 3811 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1048 AN: 3470

East Asian (EAS) AF: 0.652 AC: 3372 AN: 5170

South Asian (SAS) AF: 0.523 AC: 2523 AN: 4824

European-Finnish (FIN) AF: 0.325 AC: 3433 AN: 10564

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25137 AN: 67970

Other (OTH) AF: 0.298 AC: 627 AN: 2106

Alfa AF: 0.202 Hom.: 498

Bravo AF: 0.281

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.38
DANN	Benign	0.85
PhyloP100		-0.041

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: rs981471; hg19: chr14-77629017;