Variant 1-93154751-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_016040.5(TMED5):c.609A>G(p.Leu203Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000813 in 1,614,130 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00083 ( 17 hom. )

Consequence

TMED5
NM_016040.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.806

Variant links:

Genes affected

TMED5 (HGNC:24251): (transmembrane p24 trafficking protein 5) Involved in Golgi ribbon formation. Located in cis-Golgi network; endoplasmic reticulum exit site; and endoplasmic reticulum-Golgi intermediate compartment. [provided by Alliance of Genome Resources, Apr 2022]

TMED5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 1-93154751-T-C is Benign according to our data. Variant chr1-93154751-T-C is described in ClinVar as [Benign]. Clinvar id is 746730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.806 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMED5	NM_016040.5 link	c.609A>G	p.Leu203Leu	synonymous_variant	4/4	ENST00000370282.8	NP_057124.3	Q9Y3A6-1
TMED5	NM_001167830.2 link	c.*76A>G		3_prime_UTR_variant	5/5		NP_001161302.1	Q9Y3A6-2
TMED5	NR_030761.2 link	n.851A>G		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMED5	ENST00000370282.8 link	c.609A>G	p.Leu203Leu	synonymous_variant	4/4	1	NM_016040.5	ENSP00000359305.3		Q9Y3A6-1

Frequencies

GnomAD3 genomes

AF:

0.000618

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00994

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00170

AC:

427

AN:

251470

Hom.:

AF XY:

0.00224

AC XY:

304

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0123

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.000833

AC:

1218

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

851

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00138

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000630

Gnomad4 OTH exome

AF:

0.000911

GnomAD4 genome

AF:

0.000617

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.000739

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00995

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000327

Hom.:

Bravo

AF:

0.000529

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 13, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

9.5

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over