6-116511734-A-T

Position:

• chr6-116511734-A-T

Variant summary

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

The NM_153711.5(CALHM5):​c.38A>T​(p.Asn13Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CALHM5 NM_153711.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.64

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]

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]

ACMG classification

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	c.38A>T	p.Asn13Ile	missense_variant	1/2	ENST00000368599.4	NP_714922.1
TRAPPC3L	NM_001139444.3	c.241-11068T>A		intron_variant		ENST00000368602.4	NP_001132916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALHM5	ENST00000368599.4	c.38A>T	p.Asn13Ile	missense_variant	1/2	1	NM_153711.5	ENSP00000357588.3
TRAPPC3L	ENST00000368602.4	c.241-11068T>A		intron_variant		5	NM_001139444.3	ENSP00000357591.3
TRAPPC3L	ENST00000437098.5	c.199-11068T>A		intron_variant		3		ENSP00000395769.1
TRAPPC3L	ENST00000356128.4	c.-13+460T>A		intron_variant		2		ENSP00000348445.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 20, 2024

The c.38A>T (p.N13I) alteration is located in exon 1 (coding exon 1) of the FAM26E gene. This alteration results from a A to T substitution at nucleotide position 38, causing the asparagine (N) at amino acid position 13 to be replaced by an isoleucine (I). 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	0.33
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	T
Eigen	Uncertain	0.63
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-1.2	T
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.20
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.011	D
Polyphen		0.87	P
Vest4		0.72
MutPred		0.43		Gain of ubiquitination at K15 (P = 0.052);
MVP		0.067
MPC		0.47
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.75
gMVP		0.78

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-116832897;