rs3014199

Variant names:

• chr10-103476168-T-C
• rs3014199
• NM_001129742.2:c.543+126A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 79 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALHM3	NM_001129742.2	MANE Select	c.543+126A>G		intron	N/A	NP_001123214.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALHM3	ENST00000369783.4	TSL:1 MANE Select	c.543+126A>G		intron	N/A	ENSP00000358798.4

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

African (AFR) AF: 0.0307 AC: 846 AN: 27528

American (AMR) AF: 0.0213 AC: 677 AN: 31850

Ashkenazi Jewish (ASJ) AF: 0.00903 AC: 184 AN: 20382

East Asian (EAS) AF: 0.000116 AC: 4 AN: 34402

South Asian (SAS) AF: 0.0250 AC: 1644 AN: 65764

European-Finnish (FIN) AF: 0.0423 AC: 1887 AN: 44584

Middle Eastern (MID) AF: 0.0133 AC: 58 AN: 4358

European-Non Finnish (NFE) AF: 0.0398 AC: 35877 AN: 900948

Other (OTH) AF: 0.0310 AC: 1553 AN: 50032

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

African (AFR) AF: 0.0278 AC: 1156 AN: 41544

American (AMR) AF: 0.0274 AC: 420 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.0201 AC: 97 AN: 4822

European-Finnish (FIN) AF: 0.0424 AC: 450 AN: 10622

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0378 AC: 2574 AN: 68016

Other (OTH) AF: 0.0288 AC: 61 AN: 2116

Alfa AF: 0.0367 Hom.: 14

Bravo AF: 0.0296

Asia WGS AF: 0.0100 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.37
PhyloP100		-0.82
Mutation Taster		=100/0	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: rs3014199; hg19: chr10-105235925;