rs360097

Positions:

• chr1-225878055-C-A
• chr1-225878055-C-G

Variant summary

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

The NM_014698.3(TMEM63A):​c.-14-461G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 151,950 control chromosomes in the GnomAD database, including 26,821 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 0.57 (26821 hom., cov: 31)
• Consequence: TMEM63A NM_014698.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.290

Genes affected

TMEM63A (HGNC:29118): (transmembrane protein 63A) Enables mechanosensitive ion channel activity. Predicted to be involved in cation transmembrane transport. Located in centriolar satellite and lysosomal membrane. Implicated in hypomyelinating leukodystrophy. [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 (NFE) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM63A	NM_014698.3	c.-14-461G>T		intron_variant		ENST00000366835.8	NP_055513.2
TMEM63A	XM_011544330.4	c.-14-461G>T		intron_variant			XP_011542632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM63A	ENST00000366835.8	c.-14-461G>T		intron_variant		1	NM_014698.3	ENSP00000355800.3

Frequencies

GnomAD3 genomes AF: 0.573 AC: 86976 AN: 151832 Hom.: 26809 Cov.: 31

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.604

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

GnomAD4 genome AF: 0.573 AC: 87008 AN: 151950 Hom.: 26821 Cov.: 31 AF XY: 0.578 AC XY: 42950 AN XY: 74264

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.630

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.794

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.604

Alfa AF: 0.656 Hom.: 43682

Bravo AF: 0.554

Asia WGS AF: 0.474 AC: 1649 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	2.1
DANN	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs360097; hg19: chr1-226065755;