rs2033345342

Variant names:

• chr10-103473347-G-A
• rs2033345342
• NM_001129742.2:c.901C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-103473347-G-A
• chr10-103473347-G-C

Variant summary

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

The NM_001129742.2(CALHM3):​c.901C>T​(p.Leu301Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000369 in 1,353,584 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L301P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: CALHM3 NM_001129742.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.85
• Publications: 0 publications found

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]

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_001129742.2. 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
	CALHM3	NM_001129742.2	MANE Select	c.901C>T	p.Leu301Phe	missense	Exon 3 of 3	NP_001123214.1	Q86XJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALHM3	ENST00000369783.4	TSL:1 MANE Select	c.901C>T	p.Leu301Phe	missense	Exon 3 of 3	ENSP00000358798.4	Q86XJ0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000369 AC: 5 AN: 1353584 Hom.: 0 Cov.: 29 AF XY: 0.00000605 AC XY: 4 AN XY: 661696

African (AFR) AF: 0.0000331 AC: 1 AN: 30216

American (AMR) AF: 0.00 AC: 0 AN: 30802

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22414

East Asian (EAS) AF: 0.00 AC: 0 AN: 35180

South Asian (SAS) AF: 0.00 AC: 0 AN: 72284

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5502

European-Non Finnish (NFE) AF: 0.00000380 AC: 4 AN: 1053736

Other (OTH) AF: 0.00 AC: 0 AN: 55912

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.88	T
PhyloP100		3.9
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.14
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.019	D
Vest4		0.53
MutPred		0.35		Loss of stability (P = 0.0441)
MVP		0.24
ClinPred		0.97	D
GERP RS		5.7
Varity_R		0.29
gMVP		0.52
Mutation Taster		=51/49	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: rs2033345342; hg19: chr10-105233104;