5-115616227-TG-AA

Variant names:

• chr5-115616227-TG-AA
• NM_181836.6:c.656_657delCAinsTT
• TMED7 p.Thr219Ile

Variant summary

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

The NM_181836.6(TMED7):​c.656_657delCAinsTT​(p.Thr219Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T219R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMED7 NM_181836.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.52
• Publications: 0 publications found

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-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]

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

ACMG classification

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMED7	NM_181836.6	MANE Select	c.656_657delCAinsTT	p.Thr219Ile	missense	N/A	NP_861974.1	Q9Y3B3-1
	TMED7-TICAM2	NM_001164468.4		c.566+90_566+91delCAinsTT		intron	N/A	NP_001157940.1
	TMED7-TICAM2	NM_001164469.4		c.566+90_566+91delCAinsTT		intron	N/A	NP_001157941.1	A0A0A6YYA0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMED7	ENST00000456936.4	TSL:1 MANE Select	c.656_657delCAinsTT	p.Thr219Ile	missense	N/A	ENSP00000405926.3	Q9Y3B3-1
	TMED7-TICAM2	ENST00000282382.8	TSL:2	c.566+90_566+91delCAinsTT		intron	N/A	ENSP00000282382.4
	TMED7	ENST00000878959.1		c.656_657delCAinsTT	p.Thr219Ile	missense	N/A	ENSP00000549018.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-114951924;