Genetic Variant CALHM6:p.Leu111Pro (chr6-116462261-T-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001010919.3(CALHM6):c.332T>C(p.Leu111Pro) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CALHM6
NM_001010919.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39

Publications

0 publications found

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 links:

ENSG00000285446 (HGNC:):

ENSG00000285446 links:

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

CALHM6-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.757

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010919.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CALHM6	NM_001010919.3	MANE Select	c.332T>C	p.Leu111Pro	missense	Exon 2 of 3	NP_001010919.1	Q5R3K3-1
CALHM6	NM_001276460.2		c.9+832T>C		intron	N/A	NP_001263389.1	Q5R3K3-2
CALHM6-AS1	NR_174951.1		n.87-1067A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CALHM6	ENST00000368605.3	TSL:5 MANE Select	c.332T>C	p.Leu111Pro	missense	Exon 2 of 3	ENSP00000357594.1	Q5R3K3-1
ENSG00000285446	ENST00000644499.1		c.767-1022T>C		intron	N/A	ENSP00000495266.1	A0A2R8Y6J1
CALHM6	ENST00000859968.1		c.332T>C	p.Leu111Pro	missense	Exon 1 of 2	ENSP00000530027.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1223992

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

593658

African (AFR)

AF:

0.00

AC:

AN:

24310

American (AMR)

AF:

0.00

AC:

AN:

12042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17388

East Asian (EAS)

AF:

0.00

AC:

AN:

27388

South Asian (SAS)

AF:

0.00

AC:

AN:

54710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29860

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3506

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1004272

Other (OTH)

AF:

0.00

AC:

AN:

50516

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.046

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.60

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.76

MetaSVM

Benign

-1.1

PhyloP100

1.4

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-4.9

REVEL

Benign

0.27

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.67

MutPred

0.66

Loss of catalytic residue at L111 (P = 0.0077)

MVP

0.32

MPC

0.58

ClinPred

0.94

GERP RS

2.6

PromoterAI

0.076

Neutral

(source)

Varity_R

0.79

gMVP

0.77

Mutation Taster

=74/26

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over