1-225848608-A-G

Position:

• chr1-225848608-A-G

Variant summary

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

The ENST00000366835.8(TMEM63A):​c.2188-54T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 1,579,976 control chromosomes in the GnomAD database, including 298,732 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 0.65 (32516 hom., cov: 32)
  • Exomes 𝑓: 0.61 (266216 hom.)
• Consequence: TMEM63A ENST00000366835.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM63A	NM_014698.3	c.2188-54T>C		intron_variant		ENST00000366835.8	NP_055513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM63A	ENST00000366835.8	c.2188-54T>C		intron_variant		1	NM_014698.3	ENSP00000355800	P1
TMEM63A	ENST00000482753.1	n.93-54T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98061 AN: 151894 Hom.: 32468 Cov.: 32

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.636

GnomAD4 exome AF: 0.609 AC: 868916 AN: 1427964 Hom.: 266216 AF XY: 0.611 AC XY: 435200 AN XY: 712460

Gnomad4 AFR exome AF: 0.789

Gnomad4 AMR exome AF: 0.531

Gnomad4 ASJ exome AF: 0.543

Gnomad4 EAS exome AF: 0.661

Gnomad4 SAS exome AF: 0.692

Gnomad4 FIN exome AF: 0.523

Gnomad4 NFE exome AF: 0.603

Gnomad4 OTH exome AF: 0.618

GnomAD4 genome AF: 0.646 AC: 98164 AN: 152012 Hom.: 32516 Cov.: 32 AF XY: 0.639 AC XY: 47498 AN XY: 74302

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.604

Gnomad4 OTH AF: 0.638

Alfa AF: 0.618 Hom.: 23113

Bravo AF: 0.652

Asia WGS AF: 0.724 AC: 2517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.15
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs360063; hg19: chr1-226036309; COSMIC: COSV55298940; COSMIC: COSV55298940;