chr5-115616462-T-C

Variant names:

• chr5-115616462-T-C
• rs1756750335
• NM_181836.6:c.439-17A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_181836.6(TMED7):​c.439-17A>G variant causes a intron 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMED7 NM_181836.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0150
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 5-115616462-T-C is Benign according to our data. Variant chr5-115616462-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2104096.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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMED7	NM_181836.6	MANE Select	c.439-17A>G		intron	N/A	NP_861974.1	Q9Y3B3-1
	TMED7-TICAM2	NM_001164468.4		c.439-17A>G		intron	N/A	NP_001157940.1
	TMED7-TICAM2	NM_001164469.4		c.439-17A>G		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.439-17A>G		intron	N/A	ENSP00000405926.3	Q9Y3B3-1
	TMED7-TICAM2	ENST00000282382.8	TSL:2	c.439-17A>G		intron	N/A	ENSP00000282382.4
	TMED7	ENST00000878959.1		c.439-17A>G		intron	N/A	ENSP00000549018.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	10
DANN	Benign	0.76
PhyloP100		-0.015

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

Other links and lift over

dbSNP: rs1756750335; hg19: chr5-114952159;