rs9372465

Variant names:

• chr6-116540720-G-C
• rs9372465
• NM_001139444.3:c.141-258C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-116540720-G-C
• chr6-116540720-G-T

Variant summary

Our verdict is Benign. The variant received -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. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001139444.3. 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
	TRAPPC3L	NM_001139444.3	MANE Select	c.141-258C>G		intron	N/A	NP_001132916.1
	CALHM4	NM_001256887.3		c.-140-3045G>C		intron	N/A	NP_001243816.1
	CALHM4	NM_001256888.3		c.-49-3045G>C		intron	N/A	NP_001243817.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC3L	ENST00000368602.4	TSL:5 MANE Select	c.141-258C>G		intron	N/A	ENSP00000357591.3
	CALHM4	ENST00000405399.5	TSL:1	c.-140-3045G>C		intron	N/A	ENSP00000385836.1
	CALHM4	ENST00000368597.6	TSL:1	c.-108-3045G>C		intron	N/A	ENSP00000357586.2

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

African (AFR) AF: 0.728 AC: 30162 AN: 41418

American (AMR) AF: 0.736 AC: 11231 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2644 AN: 3466

East Asian (EAS) AF: 0.892 AC: 4602 AN: 5160

South Asian (SAS) AF: 0.667 AC: 3198 AN: 4798

European-Finnish (FIN) AF: 0.688 AC: 7246 AN: 10534

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.641 AC: 43500 AN: 67904

Other (OTH) AF: 0.705 AC: 1484 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.48
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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