6-116512006-A-G

Variant names:

• chr6-116512006-A-G
• rs1363970144
• NM_153711.5:c.310A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153711.5(CALHM5):​c.310A>G​(p.Thr104Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CALHM5 NM_153711.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.81
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1683285).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153711.5. 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
	CALHM5	NM_153711.5	MANE Select	c.310A>G	p.Thr104Ala	missense	Exon 1 of 2	NP_714922.1	Q8N5C1
	TRAPPC3L	NM_001139444.3	MANE Select	c.241-11340T>C		intron	N/A	NP_001132916.1	Q5T215-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALHM5	ENST00000368599.4	TSL:1 MANE Select	c.310A>G	p.Thr104Ala	missense	Exon 1 of 2	ENSP00000357588.3	Q8N5C1
	TRAPPC3L	ENST00000368602.4	TSL:5 MANE Select	c.241-11340T>C		intron	N/A	ENSP00000357591.3	Q5T215-1
	TRAPPC3L	ENST00000437098.5	TSL:3	c.199-11340T>C		intron	N/A	ENSP00000395769.1	A0A0A0MSL6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Benign	0.091
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.8
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.095
Sift	Benign	0.38	T
Sift4G	Benign	0.28	T
Polyphen		0.29	B
Vest4		0.25
MutPred		0.35		Gain of helix (P = 0.1736)
MVP		0.072
MPC		0.10
ClinPred		0.76	D
GERP RS		5.5
PromoterAI		0.065	Neutral
Varity_R		0.074
gMVP		0.41
Mutation Taster		=74/26	polymorphism

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: rs1363970144; hg19: chr6-116833169;