chr1-225878055-C-A

Variant names:

• chr1-225878055-C-A
• rs360097
• NM_014698.3:c.-14-461G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

TMEM63A Gene-Disease associations (from GenCC):

• leukodystrophy, hypomyelinating, 19, transient infantile

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

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 (NFE) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM63A	NM_014698.3	c.-14-461G>T		intron_variant	Intron 2 of 24	ENST00000366835.8	NP_055513.2
TMEM63A	XM_011544330.4	c.-14-461G>T		intron_variant	Intron 1 of 23		XP_011542632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM63A	ENST00000366835.8	c.-14-461G>T		intron_variant	Intron 2 of 24	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

African (AFR) AF: 0.335 AC: 13889 AN: 41416

American (AMR) AF: 0.630 AC: 9623 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2492 AN: 3468

East Asian (EAS) AF: 0.466 AC: 2399 AN: 5148

South Asian (SAS) AF: 0.510 AC: 2463 AN: 4826

European-Finnish (FIN) AF: 0.794 AC: 8381 AN: 10554

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.671 AC: 45594 AN: 67968

Other (OTH) AF: 0.604 AC: 1270 AN: 2102

Alfa AF: 0.647 Hom.: 54295

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
PhyloP100		0.29
PromoterAI		0.076	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs360097; hg19: chr1-226065755; COSMIC: COSV107472072; COSMIC: COSV107472072;