rs3738051

Positions:

• chr1-225855773-A-G

Variant summary

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

The NM_014698.3(TMEM63A):​c.1634+105T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0467 in 1,155,110 control chromosomes in the GnomAD database, including 1,727 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 0.042 (206 hom., cov: 32)
  • Exomes 𝑓: 0.047 (1521 hom.)
• Consequence: TMEM63A NM_014698.3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM63A	NM_014698.3	c.1634+105T>C		intron_variant		ENST00000366835.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM63A	ENST00000366835.8	c.1634+105T>C		intron_variant		1	NM_014698.3	P1

Frequencies

GnomAD3 genomes AF: 0.0414 AC: 6302 AN: 152196 Hom.: 200 Cov.: 32

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0466

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.0772

Gnomad FIN AF: 0.0813

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0401

Gnomad OTH AF: 0.0458

GnomAD4 exome AF: 0.0475 AC: 47592 AN: 1002796 Hom.: 1521 AF XY: 0.0482 AC XY: 24418 AN XY: 506940

Gnomad4 AFR exome AF: 0.0120

Gnomad4 AMR exome AF: 0.0573

Gnomad4 ASJ exome AF: 0.0573

Gnomad4 EAS exome AF: 0.152

Gnomad4 SAS exome AF: 0.0770

Gnomad4 FIN exome AF: 0.0793

Gnomad4 NFE exome AF: 0.0382

Gnomad4 OTH exome AF: 0.0499

GnomAD4 genome AF: 0.0416 AC: 6336 AN: 152314 Hom.: 206 Cov.: 32 AF XY: 0.0437 AC XY: 3256 AN XY: 74474

Gnomad4 AFR AF: 0.0133

Gnomad4 AMR AF: 0.0468

Gnomad4 ASJ AF: 0.0634

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.0774

Gnomad4 FIN AF: 0.0813

Gnomad4 NFE AF: 0.0401

Gnomad4 OTH AF: 0.0506

Alfa AF: 0.0385 Hom.: 14

Bravo AF: 0.0376

Asia WGS AF: 0.133 AC: 461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.0080
DANN	Benign	0.52

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: rs3738051; hg19: chr1-226043474; COSMIC: COSV64764124; COSMIC: COSV64764124;