6-116462196-C-G

Variant names:

• chr6-116462196-C-G
• NM_001010919.3:c.267C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001010919.3(CALHM6):​c.267C>G​(p.Cys89Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,353,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: CALHM6 NM_001010919.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.964

Genes affected

CALHM6 (HGNC:33391): (calcium homeostasis modulator family member 6) 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]

ENSG00000285446 (HGNC:):

CALHM6-AS1 (HGNC:40971): (CALHM6 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26496482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALHM6	NM_001010919.3	c.267C>G	p.Cys89Trp	missense_variant	Exon 2 of 3	ENST00000368605.3	NP_001010919.1
CALHM6	XM_011535845.4	c.267C>G	p.Cys89Trp	missense_variant	Exon 1 of 2		XP_011534147.1
CALHM6	NM_001276460.2	c.9+767C>G		intron_variant	Intron 1 of 1		NP_001263389.1
CALHM6-AS1	NR_174951.1	n.87-1002G>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALHM6	ENST00000368605.3	c.267C>G	p.Cys89Trp	missense_variant	Exon 2 of 3	5	NM_001010919.3	ENSP00000357594.1
ENSG00000285446	ENST00000644499.1	c.767-1087C>G		intron_variant	Intron 3 of 3			ENSP00000495266.1
CALHM6	ENST00000368606.7	c.9+767C>G		intron_variant	Intron 1 of 1	3		ENSP00000357595.3
CALHM6-AS1	ENST00000476099.1	n.75-1002G>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000148 AC: 2 AN: 1353900 Hom.: 0 Cov.: 37 AF XY: 0.00000300 AC XY: 2 AN XY: 666564

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000264

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.267C>G (p.C89W) alteration is located in exon 2 (coding exon 1) of the FAM26F gene. This alteration results from a C to G substitution at nucleotide position 267, causing the cysteine (C) at amino acid position 89 to be replaced by a tryptophan (W). 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	0.17
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.79
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.060
Sift	Benign	0.18	T
Sift4G	Benign	0.17	T
Polyphen		1.0	D
Vest4		0.38
MutPred		0.46		Gain of MoRF binding (P = 0.0086);
MVP		0.18
MPC		0.54
ClinPred		0.78	D
GERP RS		2.8
Varity_R		0.12
gMVP		0.55

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: chr6-116783359;