19-10835315-CA-TT

Variant names:

• chr19-10835315-CA-TT
• NM_006858.4:c.221_222delTGinsAA
• TMED1 p.Leu74Gln

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_006858.4(TMED1):​c.221_222delTGinsAA​(p.Leu74Gln) variant causes a missense change involving the alteration of a conserved nucleotide. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMED1 NM_006858.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.75
• Publications: 0 publications found

Genes affected

TMED1 (HGNC:17291): (transmembrane p24 trafficking protein 1) This gene belongs to the TMED (transmembrane emp24 domain-containing) protein family, which is involved in the vesicular trafficking of proteins. The protein encoded by this gene was identified by its interaction with interleukin 1 receptor-like 1 (IL1RL1) and may play a role in innate immunity. This protein lacks any similarity to other interleukin 1 ligands. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006858.4. 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
	TMED1	NM_006858.4	MANE Select	c.221_222delTGinsAA	p.Leu74Gln	missense	N/A	NP_006849.1	Q13445
	TMED1	NR_104015.2		n.176_177delTGinsAA		non_coding_transcript_exon	Exon 2 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMED1	ENST00000214869.7	TSL:1 MANE Select	c.221_222delTGinsAA	p.Leu74Gln	missense	N/A	ENSP00000214869.1	Q13445
	TMED1	ENST00000589638.1	TSL:5	c.221_222delTGinsAA	p.Leu74Gln	missense	N/A	ENSP00000467690.1	K7EQ63
	TMED1	ENST00000591695.5	TSL:5	c.221_222delTGinsAA	p.Leu74Gln	missense	N/A	ENSP00000468294.1	K7ERK5

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.8

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: chr19-10945991;