Variant 6-116512039-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153711.5(CALHM5):c.343C>G(p.Leu115Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,888 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CALHM5
NM_153711.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.34

Variant links:

Genes affected

CALHM5 (HGNC:21568): (calcium homeostasis modulator family member 5) Predicted to enable cation channel activity. Predicted to be involved in cation transmembrane transport. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CALHM5 links:

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]

TRAPPC3L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALHM5	NM_153711.5 linkuse as main transcript	c.343C>G	p.Leu115Val	missense_variant	1/2	ENST00000368599.4	NP_714922.1	Q8N5C1
TRAPPC3L	NM_001139444.3 linkuse as main transcript	c.241-11373G>C		intron_variant		ENST00000368602.4	NP_001132916.1	Q5T215-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CALHM5	ENST00000368599.4 linkuse as main transcript	c.343C>G	p.Leu115Val	missense_variant	1/2	1	NM_153711.5	ENSP00000357588.3	Q8N5C1
TRAPPC3L	ENST00000368602.4 linkuse as main transcript	c.241-11373G>C		intron_variant		5	NM_001139444.3	ENSP00000357591.3	Q5T215-1
TRAPPC3L	ENST00000437098.5 linkuse as main transcript	c.199-11373G>C		intron_variant		3		ENSP00000395769.1	A0A0A0MSL6
TRAPPC3L	ENST00000356128.4 linkuse as main transcript	c.-13+155G>C		intron_variant		2		ENSP00000348445.4	Q5T215-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250942

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135610

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461752

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000179

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

AF:

0.00000657

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 11, 2024

The c.343C>G (p.L115V) alteration is located in exon 1 (coding exon 1) of the FAM26E gene. This alteration results from a C to G substitution at nucleotide position 343, causing the leucine (L) at amino acid position 115 to be replaced by a valine (V). 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

0.14

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0043

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.58

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.40

REVEL

Benign

0.13

Sift

Benign

0.24

Sift4G

Benign

0.29

Polyphen

0.98

Vest4

0.71

MutPred

0.37

Gain of catalytic residue at L115 (P = 0.029);

MVP

0.085

MPC

0.49

ClinPred

0.57

GERP RS

5.3

Varity_R

0.19

gMVP

0.54

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over