6-116557838-T-A

Variant names:

• chr6-116557838-T-A
• rs776070502
• NM_001366078.2:c.572T>A

Variant summary

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

The NM_001366078.2(CALHM4):​c.572T>A​(p.Ile191Asn) variant causes a missense change involving the alteration of a non-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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I191T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CALHM4 NM_001366078.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.49
• Publications: 1 publications found

Genes affected

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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366078.2. 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
	CALHM4	NM_001366078.2	MANE Select	c.572T>A	p.Ile191Asn	missense	Exon 2 of 2	NP_001353007.1	Q5JW98-1
	CALHM4	NM_001256887.3		c.143T>A	p.Ile48Asn	missense	Exon 4 of 4	NP_001243816.1	Q5JW98-3
	CALHM4	NM_001256888.3		c.140T>A	p.Ile47Asn	missense	Exon 4 of 4	NP_001243817.1	Q5JW98-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALHM4	ENST00000368596.4	TSL:5 MANE Select	c.572T>A	p.Ile191Asn	missense	Exon 2 of 2	ENSP00000357585.3	Q5JW98-1
	CALHM4	ENST00000405399.5	TSL:1	c.143T>A	p.Ile48Asn	missense	Exon 4 of 4	ENSP00000385836.1	Q5JW98-3
	CALHM4	ENST00000368597.6	TSL:1	c.14T>A	p.Ile5Asn	missense	Exon 3 of 3	ENSP00000357586.2	Q5JW98-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.1	T
PhyloP100		2.5
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.22
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.96	D
Vest4		0.72
MutPred		0.61		Loss of stability (P = 0.0656)
MVP		0.24
MPC		0.53
ClinPred		0.99	D
GERP RS		3.3
Varity_R		0.77
gMVP		0.31
Mutation Taster		=67/33	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: rs776070502; hg19: chr6-116879001;