5-115616314-T-A

Variant names:

• chr5-115616314-T-A
• rs1058047
• NM_181836.6:c.570A>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001164468.4(TMED7-TICAM2):​c.566+4A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 1,614,188 control chromosomes in the GnomAD database, including 289 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (19 hom., cov: 33)
  • Exomes 𝑓: 0.017 (270 hom.)
• Consequence: TMED7-TICAM2 NM_001164468.4 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.235

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 5-115616314-T-A is Benign according to our data. Variant chr5-115616314-T-A is described in ClinVar as [Benign]. Clinvar id is 1657409.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0127 (1931/152342) while in subpopulation NFE AF= 0.0166 (1132/68018). AF 95% confidence interval is 0.0158. There are 19 homozygotes in gnomad4. There are 920 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMED7	NM_181836.6	c.570A>T	p.Ser190Ser	synonymous_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.570A>T	p.Ser190Ser	synonymous_variant	Exon 3 of 3	1	NM_181836.6	ENSP00000405926.3
TMED7-TICAM2	ENST00000282382.8	c.566+4A>T		splice_region_variant, intron_variant	Intron 3 of 3	2		ENSP00000282382.4

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1932 AN: 152224 Hom.: 19 Cov.: 33

Gnomad AFR AF: 0.00321

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0145

Gnomad ASJ AF: 0.0593

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.0104

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.0268

GnomAD3 exomes AF: 0.0144 AC: 3588 AN: 249374 Hom.: 53 AF XY: 0.0148 AC XY: 1991 AN XY: 134980

Gnomad AFR exome AF: 0.00240

Gnomad AMR exome AF: 0.00989

Gnomad ASJ exome AF: 0.0525

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00676

Gnomad FIN exome AF: 0.0160

Gnomad NFE exome AF: 0.0179

Gnomad OTH exome AF: 0.0201

GnomAD4 exome AF: 0.0169 AC: 24674 AN: 1461846 Hom.: 270 Cov.: 31 AF XY: 0.0168 AC XY: 12223 AN XY: 727222

Gnomad4 AFR exome AF: 0.00275

Gnomad4 AMR exome AF: 0.0106

Gnomad4 ASJ exome AF: 0.0524

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00691

Gnomad4 FIN exome AF: 0.0165

Gnomad4 NFE exome AF: 0.0180

Gnomad4 OTH exome AF: 0.0175

GnomAD4 genome AF: 0.0127 AC: 1931 AN: 152342 Hom.: 19 Cov.: 33 AF XY: 0.0123 AC XY: 920 AN XY: 74508

Gnomad4 AFR AF: 0.00320

Gnomad4 AMR AF: 0.0145

Gnomad4 ASJ AF: 0.0593

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00414

Gnomad4 FIN AF: 0.0104

Gnomad4 NFE AF: 0.0166

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0202 Hom.: 20

Bravo AF: 0.0134

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.0192

EpiControl AF: 0.0184

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	7.6
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.58		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: -42
DS_DL_spliceai		0.58		Position offset: 4

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

Publications

LitVar

Other links and lift over

dbSNP: rs1058047; hg19: chr5-114952011; COSMIC: COSV56695251; COSMIC: COSV56695251;