rs2986034

Positions:

• chr10-103472823-G-A
• chr10-103472823-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001129742.2(CALHM3):​c.*390C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 181,208 control chromosomes in the GnomAD database, including 47,727 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.71 (39454 hom., cov: 31)
  • Exomes 𝑓: 0.74 (8273 hom.)
• Consequence: CALHM3 NM_001129742.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALHM3	NM_001129742.2	c.*390C>T		3_prime_UTR_variant	3/3	ENST00000369783.4	NP_001123214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALHM3	ENST00000369783.4	c.*390C>T		3_prime_UTR_variant	3/3	1	NM_001129742.2	ENSP00000358798	P1

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108612 AN: 151964 Hom.: 39435 Cov.: 31

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.858

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.728

GnomAD4 exome AF: 0.743 AC: 21627 AN: 29126 Hom.: 8273 Cov.: 0 AF XY: 0.745 AC XY: 10760 AN XY: 14448

Gnomad4 AFR exome AF: 0.567

Gnomad4 AMR exome AF: 0.809

Gnomad4 ASJ exome AF: 0.748

Gnomad4 EAS exome AF: 0.840

Gnomad4 SAS exome AF: 0.909

Gnomad4 FIN exome AF: 0.762

Gnomad4 NFE exome AF: 0.739

Gnomad4 OTH exome AF: 0.737

GnomAD4 genome AF: 0.715 AC: 108676 AN: 152082 Hom.: 39454 Cov.: 31 AF XY: 0.720 AC XY: 53515 AN XY: 74352

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.785

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.790

Gnomad4 SAS AF: 0.858

Gnomad4 FIN AF: 0.791

Gnomad4 NFE AF: 0.751

Gnomad4 OTH AF: 0.730

Alfa AF: 0.747 Hom.: 41233

Bravo AF: 0.708

Asia WGS AF: 0.834 AC: 2900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.40
DANN	Benign	0.37

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

Other links and lift over

dbSNP: rs2986034; hg19: chr10-105232580;