rs2740174

Positions:

• chr1-225846268-A-G
• chr1-225846268-A-T

Variant summary

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

The NM_014698.3(TMEM63A):​c.*671T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,606 control chromosomes in the GnomAD database, including 1,007 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 0.11 (1004 hom., cov: 33)
  • Exomes 𝑓: 0.098 (3 hom.)
• Consequence: TMEM63A NM_014698.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.700

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]

ENSG00000242861 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM63A	NM_014698.3	c.*671T>C		3_prime_UTR_variant	25/25	ENST00000366835.8	NP_055513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM63A	ENST00000366835	c.*671T>C		3_prime_UTR_variant	25/25	1	NM_014698.3	ENSP00000355800.3
ENSG00000242861	ENST00000424332.1	n.43+212T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16258 AN: 152192 Hom.: 1002 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0758

Gnomad ASJ AF: 0.0862

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.0626

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.0980 AC: 29 AN: 296 Hom.: 3 Cov.: 0 AF XY: 0.113 AC XY: 24 AN XY: 212

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.0992

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.107 AC: 16270 AN: 152310 Hom.: 1004 Cov.: 33 AF XY: 0.105 AC XY: 7839 AN XY: 74470

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.0757

Gnomad4 ASJ AF: 0.0862

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.0626

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.111

Alfa AF: 0.108 Hom.: 1881

Bravo AF: 0.103

Asia WGS AF: 0.169 AC: 588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.17
DANN	Benign	0.75

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: rs2740174; hg19: chr1-226033969;