Genetic Variant CALHM3:p.Asp299His (chr10-103473353-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001129742.2(CALHM3):c.895G>C(p.Asp299His) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CALHM3
NM_001129742.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.34

Publications

27 publications found

Variant links:

Genes affected

CALHM3 (HGNC:23458): (calcium homeostasis modulator 3) Predicted to enable cation channel activity. Predicted to be involved in ATP transport. Predicted to be located in basolateral plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CALHM3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37249297).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALHM3	NM_001129742.2 link	c.895G>C	p.Asp299His	missense_variant	Exon 3 of 3	ENST00000369783.4	NP_001123214.1	Q86XJ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALHM3	ENST00000369783.4 link	c.895G>C	p.Asp299His	missense_variant	Exon 3 of 3	1	NM_001129742.2	ENSP00000358798.4		Q86XJ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1348782

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

658734

African (AFR)

AF:

0.00

AC:

AN:

30078

American (AMR)

AF:

0.00

AC:

AN:

30208

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22216

East Asian (EAS)

AF:

0.00

AC:

AN:

35058

South Asian (SAS)

AF:

0.00

AC:

AN:

71618

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5476

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1051024

Other (OTH)

AF:

0.00

AC:

AN:

55716

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

191319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

0.024

Eigen_PC

Benign

-0.010

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.76

M_CAP

Benign

0.024

MetaRNN

Benign

0.37

MetaSVM

Benign

-1.0

PhyloP100

1.3

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.15

REVEL

Benign

0.067

Sift

Uncertain

0.013

Sift4G

Uncertain

0.0060

Vest4

0.18

MutPred

0.27

Gain of MoRF binding (P = 0.0492);

MVP

0.16

ClinPred

0.76

GERP RS

-0.34

Varity_R

0.10

gMVP

0.55

Mutation Taster

=75/25

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over