6-116462083-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001010919.3(CALHM6):​c.154G>A​(p.Gly52Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000168 in 1,546,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

CALHM6
NM_001010919.3 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04
Variant links:
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]
CALHM6-AS1 (HGNC:40971): (CALHM6 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12921062).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CALHM6NM_001010919.3 linkc.154G>A p.Gly52Ser missense_variant Exon 2 of 3 ENST00000368605.3 NP_001010919.1 Q5R3K3-1
CALHM6XM_011535845.4 linkc.154G>A p.Gly52Ser missense_variant Exon 1 of 2 XP_011534147.1
CALHM6NM_001276460.2 linkc.9+654G>A intron_variant Intron 1 of 1 NP_001263389.1 Q5R3K3-2
CALHM6-AS1NR_174951.1 linkn.87-889C>T intron_variant Intron 1 of 1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CALHM6ENST00000368605.3 linkc.154G>A p.Gly52Ser missense_variant Exon 2 of 3 5 NM_001010919.3 ENSP00000357594.1 Q5R3K3-1
ENSG00000285446ENST00000644499.1 linkc.767-1200G>A intron_variant Intron 3 of 3 ENSP00000495266.1 A0A2R8Y6J1
CALHM6ENST00000368606.7 linkc.9+654G>A intron_variant Intron 1 of 1 3 ENSP00000357595.3 Q5R3K3-2
CALHM6-AS1ENST00000476099.1 linkn.75-889C>T intron_variant Intron 1 of 1 2

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152090
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000620
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000675
AC:
10
AN:
148178
Hom.:
0
AF XY:
0.0000253
AC XY:
2
AN XY:
78946
show subpopulations
Gnomad AFR exome
AF:
0.000122
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000398
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000165
AC:
23
AN:
1394390
Hom.:
0
Cov.:
33
AF XY:
0.00000727
AC XY:
5
AN XY:
687762
show subpopulations
Gnomad4 AFR exome
AF:
0.0000317
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000190
Gnomad4 FIN exome
AF:
0.0000219
Gnomad4 NFE exome
AF:
0.00000371
Gnomad4 OTH exome
AF:
0.0000345
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152208
Hom.:
0
Cov.:
31
AF XY:
0.0000269
AC XY:
2
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000221
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 17, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.154G>A (p.G52S) alteration is located in exon 2 (coding exon 1) of the FAM26F gene. This alteration results from a G to A substitution at nucleotide position 154, causing the glycine (G) at amino acid position 52 to be replaced by a serine (S). 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
0.21
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.064
T
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.38
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.70
T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-1.0
T
PrimateAI
Uncertain
0.48
T
PROVEAN
Uncertain
-4.1
D
REVEL
Benign
0.18
Sift
Benign
0.30
T
Sift4G
Benign
0.31
T
Polyphen
0.97
D
Vest4
0.40
MutPred
0.52
Gain of glycosylation at G52 (P = 0.036);
MVP
0.30
MPC
0.21
ClinPred
0.67
D
GERP RS
-0.24
Varity_R
0.25
gMVP
0.69

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.

Other links and lift over

dbSNP: rs562961955; hg19: chr6-116783246; API