X-34636660-T-C

Variant names:

• chrX-34636660-T-C
• rs6628886
• NM_031442.4:c.367+2587A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031442.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM47	NM_031442.4	MANE Select	c.367+2587A>G		intron	N/A	NP_113630.1	Q9BQJ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM47	ENST00000275954.4	TSL:1 MANE Select	c.367+2587A>G		intron	N/A	ENSP00000275954.3	Q9BQJ4
	TMEM47	ENST00000876538.1		c.227-6169A>G		intron	N/A	ENSP00000546597.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 31791 AN: 110891 Hom.: 3442 Cov.: 23

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

African (AFR) AF: 0.263 AC: 8037 AN: 30553

American (AMR) AF: 0.341 AC: 3567 AN: 10453

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 873 AN: 2632

East Asian (EAS) AF: 0.629 AC: 2158 AN: 3429

South Asian (SAS) AF: 0.518 AC: 1344 AN: 2595

European-Finnish (FIN) AF: 0.232 AC: 1386 AN: 5973

Middle Eastern (MID) AF: 0.261 AC: 57 AN: 218

European-Non Finnish (NFE) AF: 0.259 AC: 13720 AN: 52897

Other (OTH) AF: 0.324 AC: 491 AN: 1515

Alfa AF: 0.270 Hom.: 1923

Bravo AF: 0.297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.33
DANN	Benign	0.76
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6628886; hg19: chrX-34654777;