rs10522027

Positions:

• chrX-34630163-G-A
• chrX-34630163-G-C
• chrX-34630163-G-T

Variant summary

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

The NM_031442.4(TMEM47):​c.*150C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 525,871 control chromosomes in the GnomAD database, including 6,739 homozygotes. There are 24,702 hemizygotes in GnomAD. 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 0.14 (1077 hom., 5003 hem., cov: 23)
  • Exomes 𝑓: 0.17 (5662 hom. 19699 hem.)
• Consequence: TMEM47 NM_031442.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78

Genes affected

TMEM47 (HGNC:18515): (transmembrane protein 47) This gene encodes a member of the PMP22/EMP/claudin protein family. The encoded protein is localized to the ER and the plasma membrane. In dogs, transcripts of this gene exist at high levels in the brain. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM47	NM_031442.4	c.*150C>T		3_prime_UTR_variant	3/3	ENST00000275954.4	NP_113630.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM47	ENST00000275954.4	c.*150C>T		3_prime_UTR_variant	3/3	1	NM_031442.4	ENSP00000275954.3

Frequencies

GnomAD3 genomes AF: 0.143 AC: 16025 AN: 112016 Hom.: 1076 Cov.: 23 AF XY: 0.146 AC XY: 4999 AN XY: 34198

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.144

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.188

GnomAD4 exome AF: 0.174 AC: 72060 AN: 413802 Hom.: 5662 Cov.: 6 AF XY: 0.187 AC XY: 19699 AN XY: 105282

Gnomad4 AFR exome AF: 0.0507

Gnomad4 AMR exome AF: 0.324

Gnomad4 ASJ exome AF: 0.199

Gnomad4 EAS exome AF: 0.453

Gnomad4 SAS exome AF: 0.295

Gnomad4 FIN exome AF: 0.126

Gnomad4 NFE exome AF: 0.147

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.143 AC: 16026 AN: 112069 Hom.: 1077 Cov.: 23 AF XY: 0.146 AC XY: 5003 AN XY: 34261

Gnomad4 AFR AF: 0.0533

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.188

Alfa AF: 0.147 Hom.: 7641

Bravo AF: 0.155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Benign	0.82

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: rs10522027; hg19: chrX-34648280; COSMIC: COSV52068569;