chr5-65647170-T-C

Variant names:

• chr5-65647170-T-C
• rs1423259422
• NM_024941.4:c.416T>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001365342.1(TRAPPC13):​c.-56T>C variant causes a 5 prime UTR premature start codon gain change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRAPPC13 NM_001365342.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.94

Genes affected

TRAPPC13 (HGNC:25828): (trafficking protein particle complex subunit 13) Predicted to be located in cytosol. Predicted to be part of TRAPPIII protein complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.787

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC13	NM_024941.4	c.416T>C	p.Ile139Thr	missense_variant	Exon 5 of 13	ENST00000399438.8	NP_079217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC13	ENST00000399438.8	c.416T>C	p.Ile139Thr	missense_variant	Exon 5 of 13	2	NM_024941.4	ENSP00000382367.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1433336 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 710348

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 04, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.416T>C (p.I139T) alteration is located in exon 5 (coding exon 5) of the TRAPPC13 gene. This alteration results from a T to C substitution at nucleotide position 416, causing the isoleucine (I) at amino acid position 139 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;.;.;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Benign	0.0096	T
MetaRNN	Pathogenic	0.79	D;D;D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.2	M;M;M;M
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.4	D;D;D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.021	D;D;D;D
Sift4G	Benign	0.17	T;T;T;T
Polyphen		0.47	P;B;B;B
Vest4		0.84
MutPred		0.78		Gain of disorder (P = 0.0186);Gain of disorder (P = 0.0186);Gain of disorder (P = 0.0186);Gain of disorder (P = 0.0186);
MVP		0.11
MPC		0.55
ClinPred		0.97	D
GERP RS		5.4
Varity_R		0.40
gMVP		0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs1423259422; hg19: chr5-64942997;