14-77342976-A-G

Variant summary

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

The NM_213601.3(TMED8):c.760+202T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 152,042 control chromosomes in the GnomAD database, including 40,268 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 0.72 (40268 hom., cov: 30)
• Consequence: TMED8 NM_213601.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMED8	NM_213601.3	c.760+202T>C		intron_variant		ENST00000216468.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMED8	ENST00000216468.8	c.760+202T>C		intron_variant		1	NM_213601.3	P1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109709 AN: 151924 Hom.: 40221 Cov.: 30

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.722 AC: 109811 AN: 152042 Hom.: 40268 Cov.: 30 AF XY: 0.722 AC XY: 53672 AN XY: 74316

Gnomad4 AFR AF: 0.836

Gnomad4 AMR AF: 0.785

Gnomad4 ASJ AF: 0.723

Gnomad4 EAS AF: 0.602

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.661

Gnomad4 OTH AF: 0.746

Alfa AF: 0.690 Hom.: 35951

Bravo AF: 0.739

Asia WGS AF: 0.656 AC: 2281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.52
Dann	Benign	0.77

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: rs2287398; hg19: chr14-77809319;