rs17105732

Positions:

• chr14-77352904-G-A

Variant summary

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

The NM_213601.3(TMED8):​c.119-1153C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0571 in 151,980 control chromosomes in the GnomAD database, including 292 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 0.057 (292 hom., cov: 32)
• Consequence: TMED8 NM_213601.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.891

Genes affected

TMED8 (HGNC:18633): (transmembrane p24 trafficking protein family member 8)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMED8	NM_213601.3	c.119-1153C>T		intron_variant		ENST00000216468.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMED8	ENST00000216468.8	c.119-1153C>T		intron_variant		1	NM_213601.3	P1

Frequencies

GnomAD3 genomes AF: 0.0571 AC: 8672 AN: 151862 Hom.: 292 Cov.: 32

Gnomad AFR AF: 0.0862

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0400

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0363

Gnomad FIN AF: 0.0561

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0485

Gnomad OTH AF: 0.0554

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

GnomAD4 genome AF: 0.0571 AC: 8672 AN: 151980 Hom.: 292 Cov.: 32 AF XY: 0.0556 AC XY: 4134 AN XY: 74330

Gnomad4 AFR AF: 0.0860

Gnomad4 AMR AF: 0.0399

Gnomad4 ASJ AF: 0.0706

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0363

Gnomad4 FIN AF: 0.0561

Gnomad4 NFE AF: 0.0485

Gnomad4 OTH AF: 0.0549

Alfa AF: 0.0509 Hom.: 264

Bravo AF: 0.0571

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.7
DANN	Benign	0.71

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: rs17105732; hg19: chr14-77819247;