rs758155361

Variant names:

• chr19-7682306-C-T
• rs758155361
• NM_001042462.2:c.53C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-7682306-C-T
• chr19-7682306-C-A
• chr19-7682306-C-G

Variant summary

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

The NM_001042462.2(TRAPPC5):​c.53C>T​(p.Ala18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,485,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: TRAPPC5 NM_001042462.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0780
• Publications: 0 publications found

Genes affected

TRAPPC5 (HGNC:23067): (trafficking protein particle complex subunit 5) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport. Part of TRAPP complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000269711 (HGNC:):

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 (MetaRNN=0.010866791).
• BP6: Variant 19-7682306-C-T is Benign according to our data. Variant chr19-7682306-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3182007.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042462.2. 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
	TRAPPC5	NM_001042462.2	MANE Select	c.53C>T	p.Ala18Val	missense	Exon 2 of 2	NP_001035927.1	Q8IUR0
	TRAPPC5	NM_001042461.3		c.53C>T	p.Ala18Val	missense	Exon 2 of 2	NP_001035926.1	Q8IUR0
	TRAPPC5	NM_174894.3		c.53C>T	p.Ala18Val	missense	Exon 2 of 2	NP_777554.1	Q8IUR0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC5	ENST00000596148.3	TSL:1 MANE Select	c.53C>T	p.Ala18Val	missense	Exon 2 of 2	ENSP00000470262.1	Q8IUR0
	TRAPPC5	ENST00000317378.5	TSL:1	c.53C>T	p.Ala18Val	missense	Exon 2 of 2	ENSP00000316990.4	Q8IUR0
	ENSG00000269711	ENST00000597959.1	TSL:4	c.228C>T	p.Gly76Gly	synonymous	Exon 3 of 3	ENSP00000469811.1	M0QYG6

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000538 AC: 5 AN: 92872 AF XY: 0.0000577

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000253

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000487

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000308 AC: 41 AN: 1333280 Hom.: 0 Cov.: 31 AF XY: 0.0000320 AC XY: 21 AN XY: 656012

African (AFR) AF: 0.00 AC: 0 AN: 25970

American (AMR) AF: 0.0000917 AC: 2 AN: 21814

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21054

East Asian (EAS) AF: 0.00 AC: 0 AN: 32720

South Asian (SAS) AF: 0.00 AC: 0 AN: 69124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4474

European-Non Finnish (NFE) AF: 0.0000359 AC: 38 AN: 1057960

Other (OTH) AF: 0.0000182 AC: 1 AN: 54948

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152166 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74326

African (AFR) AF: 0.0000241 AC: 1 AN: 41446

American (AMR) AF: 0.000131 AC: 2 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000374 AC: 4

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.078
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.038
Sift	Benign	0.057	T
Sift4G	Benign	0.17	T
Polyphen		0.0020	B
Vest4		0.012
MutPred		0.27		Loss of disorder (P = 0.0512)
MVP		0.043
MPC		1.2
ClinPred		0.086	T
GERP RS		-1.5
PromoterAI		-0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.065
gMVP		0.59
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs758155361; hg19: chr19-7747192; COSMIC: COSV58040123; COSMIC: COSV58040123;