chr14-77343378-C-T

Variant names:

• chr14-77343378-C-T
• rs138822720
• NM_213601.3:c.560G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_213601.3(TMED8):​c.560G>A​(p.Arg187His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,614,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: TMED8 NM_213601.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.41455203).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213601.3. 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
	TMED8	NM_213601.3	MANE Select	c.560G>A	p.Arg187His	missense	Exon 5 of 6	NP_998766.1	Q6PL24
	TMED8	NM_001346131.2		c.575G>A	p.Arg192His	missense	Exon 5 of 6	NP_001333060.1
	TMED8	NM_001346133.2		c.356G>A	p.Arg119His	missense	Exon 5 of 6	NP_001333062.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMED8	ENST00000216468.8	TSL:1 MANE Select	c.560G>A	p.Arg187His	missense	Exon 5 of 6	ENSP00000216468.7	Q6PL24
	TMED8	ENST00000868372.1		c.575G>A	p.Arg192His	missense	Exon 5 of 6	ENSP00000538432.1

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152214 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000478 AC: 12 AN: 251284 AF XY: 0.0000515

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000315 AC: 46 AN: 1461854 Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24 AN XY: 727222

African (AFR) AF: 0.000418 AC: 14 AN: 33478

American (AMR) AF: 0.0000894 AC: 4 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000198 AC: 22 AN: 1111996

Other (OTH) AF: 0.0000662 AC: 4 AN: 60394

GnomAD4 genome AF: 0.000131 AC: 20 AN: 152332 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74494

African (AFR) AF: 0.000241 AC: 10 AN: 41566

American (AMR) AF: 0.0000653 AC: 1 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000228 Hom.: 0

Bravo AF: 0.000132

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000576 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	34
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.012	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.3	L
PhyloP100		7.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.22
Sift	Benign	0.29	T
Sift4G	Benign	0.53	T
Polyphen		1.0	D
Vest4		0.78
MVP		0.80
MPC		0.98
ClinPred		0.40	T
GERP RS		6.0
Varity_R		0.091
gMVP		0.62
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs138822720; hg19: chr14-77809721;