14-77366739-C-T

Variant summary

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

The NM_213601.3(TMED8):c.118+10197G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 152,204 control chromosomes in the GnomAD database, including 58,632 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 0.87 (58632 hom., cov: 31)
• Consequence: TMED8 NM_213601.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMED8	NM_213601.3	c.118+10197G>A		intron_variant		ENST00000216468.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMED8	ENST00000216468.8	c.118+10197G>A		intron_variant		1	NM_213601.3	P1

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132745 AN: 152086 Hom.: 58566 Cov.: 31

Gnomad AFR AF: 0.970

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.961

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.874

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

GnomAD4 genome AF: 0.873 AC: 132873 AN: 152204 Hom.: 58632 Cov.: 31 AF XY: 0.874 AC XY: 64993 AN XY: 74400

Gnomad4 AFR AF: 0.970

Gnomad4 AMR AF: 0.914

Gnomad4 ASJ AF: 0.893

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.962

Gnomad4 FIN AF: 0.766

Gnomad4 NFE AF: 0.807

Gnomad4 OTH AF: 0.873

Alfa AF: 0.836 Hom.: 72896

Bravo AF: 0.889

Asia WGS AF: 0.974 AC: 3387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	2.0
Dann	Benign	0.36

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: rs1544708; hg19: chr14-77833082;