chr5-115616397-C-T

Variant names:

• chr5-115616397-C-T
• rs753533691
• NM_181836.6:c.487G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_181836.6(TMED7):​c.487G>A​(p.Asp163Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TMED7 NM_181836.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.17

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2926624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMED7	NM_181836.6	c.487G>A	p.Asp163Asn	missense_variant	Exon 3 of 3	ENST00000456936.4	NP_861974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMED7	ENST00000456936.4	c.487G>A	p.Asp163Asn	missense_variant	Exon 3 of 3	1	NM_181836.6	ENSP00000405926.3
TMED7-TICAM2	ENST00000282382.8	c.487G>A	p.Asp163Asn	missense_variant	Exon 3 of 4	2		ENSP00000282382.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000803 AC: 2 AN: 248954 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 134764

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461836 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727220

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000749

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.54
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	.;.;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;.;M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.6	D;D;D
REVEL	Benign	0.23
Sift	Benign	0.14	T;D;D
Sift4G	Benign	0.13	T;T;T
Polyphen		0.94	.;.;P
Vest4		0.48
MutPred		0.54		Gain of MoRF binding (P = 0.0323);Gain of MoRF binding (P = 0.0323);Gain of MoRF binding (P = 0.0323);
MVP		0.46
MPC		1.9
ClinPred		0.95	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.43
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs753533691; hg19: chr5-114952094;