dbSNP rs766986488: TMED7:c.438+13dupA (chr5-115620421-A-AT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_181836.6(TMED7):c.438+13dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,477,794 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000038 ( 0 hom. )

Consequence

TMED7
NM_181836.6 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.17

Publications

0 publications found

Variant links:

Genes affected

TMED7 (HGNC:24253): (transmembrane p24 trafficking protein 7) 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]

TMED7 links:

TMED7-TICAM2 (HGNC:33945): (TMED7-TICAM2 readthrough) This locus represents naturally occurring read-through transcription between the neighboring transmembrane emp24 protein transport domain containing 7 (TMED7) and toll-like receptor adaptor molecule 2 (TICAM2) genes. Alternative splicing results in multiple transcript variants, one of which encodes a fusion protein that shares sequence identity with the products of each individual gene. This fusion product functions to negatively regulate the adaptor MyD88-independent toll-like receptor 4 pathway. [provided by RefSeq, Nov 2010]

TMED7-TICAM2 links:

TICAM2-AS1 (HGNC:55575): (TICAM2 antisense RNA 1)

TICAM2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 5-115620421-A-AT is Benign according to our data. Variant chr5-115620421-A-AT is described in ClinVar as Benign. ClinVar VariationId is 1916398.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181836.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMED7	NM_181836.6	MANE Select	c.438+13dupA	intron	N/A	NP_861974.1	Q9Y3B3-1
TMED7-TICAM2	NM_001164468.4		c.438+13dupA	intron	N/A	NP_001157940.1
TMED7-TICAM2	NM_001164469.4		c.438+13dupA	intron	N/A	NP_001157941.1	A0A0A6YYA0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMED7	ENST00000456936.4	TSL:1 MANE Select	c.438+13dupA	intron	N/A	ENSP00000405926.3	Q9Y3B3-1
TMED7-TICAM2	ENST00000282382.8	TSL:2	c.438+13dupA	intron	N/A	ENSP00000282382.4
TMED7	ENST00000878959.1		c.438+13dupA	intron	N/A	ENSP00000549018.1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000377

AC:

AN:

1325748

Hom.:

Cov.:

AF XY:

0.00000154

AC XY:

AN XY:

649768

show subpopulations

African (AFR)

AF:

0.000178

AC:

AN:

28138

American (AMR)

AF:

0.00

AC:

AN:

23110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19698

East Asian (EAS)

AF:

0.00

AC:

AN:

35536

South Asian (SAS)

AF:

0.00

AC:

AN:

62518

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49144

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5246

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1047824

Other (OTH)

AF:

0.00

AC:

AN:

54534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152046

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41412

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67968

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.592

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over