rs9372465

chr6-116540720-G-Cchr6-116540720-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001139444.3(TRAPPC3L):c.141-258C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 151,838 control chromosomes in the GnomAD database, including 36,596 homozygotes. 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: 𝑓 0.69 (36596 hom., cov: 30)
• Consequence: TRAPPC3L NM_001139444.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.734

Genes affected

TRAPPC3L (HGNC:21090): (trafficking protein particle complex subunit 3L) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport and intra-Golgi vesicle-mediated transport. Part of TRAPP complex. [provided by Alliance of Genome Resources, Apr 2022]

CALHM4 (HGNC:21094): (calcium homeostasis modulator family member 4) Predicted to enable cation channel activity. Predicted to be involved in cation transmembrane transport. Predicted to be integral component of membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAPPC3L	NM_001139444.3	c.141-258C>G		intron_variant		ENST00000368602.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC3L	ENST00000368602.4	c.141-258C>G		intron_variant		5	NM_001139444.3	P1

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104886 AN: 151720 Hom.: 36556 Cov.: 30

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.706

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.691 AC: 104981 AN: 151838 Hom.: 36596 Cov.: 30 AF XY: 0.696 AC XY: 51618 AN XY: 74196

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.736

Gnomad4 ASJ AF: 0.763

Gnomad4 EAS AF: 0.892

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.688

Gnomad4 NFE AF: 0.641

Gnomad4 OTH AF: 0.705

Alfa AF: 0.566 Hom.: 1736

Bravo AF: 0.702

Asia WGS AF: 0.774 AC: 2688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.1
Dann	Benign	0.48

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: rs9372465; hg19: chr6-116861883; COSMIC: COSV63987325;