rs3014199

Positions:

• chr10-103476168-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001129742.2(CALHM3):​c.543+126A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0357 in 1,332,144 control chromosomes in the GnomAD database, including 945 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 0.032 (79 hom., cov: 33)
  • Exomes 𝑓: 0.036 (866 hom.)
• Consequence: CALHM3 NM_001129742.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.820

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=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0318 (4838/152296) while in subpopulation NFE AF= 0.0378 (2574/68016). AF 95% confidence interval is 0.0366. There are 79 homozygotes in gnomad4. There are 2311 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 79 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALHM3	NM_001129742.2	c.543+126A>G		intron_variant		ENST00000369783.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALHM3	ENST00000369783.4	c.543+126A>G		intron_variant		1	NM_001129742.2	P1

Frequencies

GnomAD3 genomes AF: 0.0318 AC: 4839 AN: 152178 Hom.: 79 Cov.: 33

Gnomad AFR AF: 0.0279

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0199

Gnomad FIN AF: 0.0424

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0379

Gnomad OTH AF: 0.0291

GnomAD4 exome AF: 0.0362 AC: 42730 AN: 1179848 Hom.: 866 AF XY: 0.0357 AC XY: 20705 AN XY: 580162

Gnomad4 AFR exome AF: 0.0307

Gnomad4 AMR exome AF: 0.0213

Gnomad4 ASJ exome AF: 0.00903

Gnomad4 EAS exome AF: 0.000116

Gnomad4 SAS exome AF: 0.0250

Gnomad4 FIN exome AF: 0.0423

Gnomad4 NFE exome AF: 0.0398

Gnomad4 OTH exome AF: 0.0310

GnomAD4 genome AF: 0.0318 AC: 4838 AN: 152296 Hom.: 79 Cov.: 33 AF XY: 0.0310 AC XY: 2311 AN XY: 74462

Gnomad4 AFR AF: 0.0278

Gnomad4 AMR AF: 0.0274

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0201

Gnomad4 FIN AF: 0.0424

Gnomad4 NFE AF: 0.0378

Gnomad4 OTH AF: 0.0288

Alfa AF: 0.0368 Hom.: 13

Bravo AF: 0.0296

Asia WGS AF: 0.0100 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
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: rs3014199; hg19: chr10-105235925;