rs6628886

chrX-34636660-T-C

Variant summary

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

The NM_031442.4(TMEM47):c.367+2587A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 110,941 control chromosomes in the GnomAD database, including 3,446 homozygotes. There are 9,416 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 0.29 (3446 hom., 9416 hem., cov: 23)
• Consequence: TMEM47 NM_031442.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM47	NM_031442.4	c.367+2587A>G		intron_variant		ENST00000275954.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM47	ENST00000275954.4	c.367+2587A>G		intron_variant		1	NM_031442.4	P1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 31791 AN: 110891 Hom.: 3442 Cov.: 23 AF XY: 0.283 AC XY: 9388 AN XY: 33123

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.276

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.317

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.287 AC: 31821 AN: 110941 Hom.: 3446 Cov.: 23 AF XY: 0.284 AC XY: 9416 AN XY: 33183

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.324

Alfa AF: 0.270 Hom.: 1923

Bravo AF: 0.297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.33
Dann	Benign	0.76

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: rs6628886; hg19: chrX-34654777;