14-77354043-A-G

Position:

• chr14-77354043-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.119-2292T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,088 control chromosomes in the GnomAD database, including 4,008 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 0.22 (4008 hom., cov: 31)
• Consequence: TMED8 NM_213601.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMED8	NM_213601.3	c.119-2292T>C		intron_variant		ENST00000216468.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMED8	ENST00000216468.8	c.119-2292T>C		intron_variant		1	NM_213601.3	P1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33944 AN: 151970 Hom.: 3993 Cov.: 31

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.0431

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.224 AC: 33999 AN: 152088 Hom.: 4008 Cov.: 31 AF XY: 0.221 AC XY: 16445 AN XY: 74342

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.0426

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.220

Alfa AF: 0.217 Hom.: 791

Bravo AF: 0.233

Asia WGS AF: 0.162 AC: 562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.5
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: rs11850308; hg19: chr14-77820386;