chr15-79311362-A-T

Position:

• chr15-79311362-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007364.4(TMED3):​c.113A>T​(p.Lys38Met) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMED3 NM_007364.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.12

Genes affected

TMED3 (HGNC:28889): (transmembrane p24 trafficking protein 3) Predicted to be involved in Golgi organization; endoplasmic reticulum to Golgi vesicle-mediated transport; and intracellular protein transport. Located in Golgi apparatus; endoplasmic reticulum; and endoplasmic reticulum-Golgi intermediate compartment. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37919125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMED3	NM_007364.4	c.113A>T	p.Lys38Met	missense_variant	1/3	ENST00000299705.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMED3	ENST00000299705.10	c.113A>T	p.Lys38Met	missense_variant	1/3	1	NM_007364.4	P1
TMED3	ENST00000424155.6	c.113A>T	p.Lys38Met	missense_variant	1/3	3
TMED3	ENST00000536821.5	c.113A>T	p.Lys38Met	missense_variant	1/3	2
TMED3	ENST00000543455.1	c.113A>T	p.Lys38Met	missense_variant, NMD_transcript_variant	1/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 02, 2024

The c.113A>T (p.K38M) alteration is located in exon 1 (coding exon 1) of the TMED3 gene. This alteration results from a A to T substitution at nucleotide position 113, causing the lysine (K) at amino acid position 38 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	T;.;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.38	T;T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.5	M;M;.
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-4.0	D;D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0090	D;D;D
Polyphen		0.97	D;.;.
Vest4		0.47
MutPred		0.46		Gain of catalytic residue at K38 (P = 0);Gain of catalytic residue at K38 (P = 0);Gain of catalytic residue at K38 (P = 0);
MVP		0.60
MPC		0.48
ClinPred		0.99	D
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-79603704;