NM_213601.3:c.214C>T

Variant names:

• chr14-77346462-G-A
• NM_213601.3:c.214C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_213601.3(TMED8):​c.214C>T​(p.Pro72Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: TMED8 NM_213601.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.363
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040563464).

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.214C>T	p.Pro72Ser	missense	Exon 3 of 6	NP_998766.1	Q6PL24
	TMED8	NM_001346131.2		c.214C>T	p.Pro72Ser	missense	Exon 3 of 6	NP_001333060.1
	TMED8	NM_001346133.2		c.10C>T	p.Pro4Ser	missense	Exon 3 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.214C>T	p.Pro72Ser	missense	Exon 3 of 6	ENSP00000216468.7	Q6PL24
	TMED8	ENST00000868372.1		c.214C>T	p.Pro72Ser	missense	Exon 3 of 6	ENSP00000538432.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

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	Benign	0.076
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	17
DANN	Benign	0.90
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.36
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.0090
Sift	Benign	0.32	T
Sift4G	Benign	0.33	T
Polyphen		0.0010	B
Vest4		0.21
MutPred		0.21		Gain of phosphorylation at P72 (P = 0.0233)
MVP		0.16
MPC		0.25
ClinPred		0.17	T
GERP RS		-0.25
Varity_R		0.032
gMVP		0.30
Mutation Taster		=97/3	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

hg19: chr14-77812805;