rs34089805

Variant names:

• chr19-46608504-G-A
• rs34089805
• NM_005184.4:c.201G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-46608504-G-A
• chr19-46608504-G-T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_005184.4(CALM3):​c.201G>A​(p.Pro67Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00389 in 1,614,060 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (24 hom.)
• Consequence: CALM3 NM_005184.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.93
• Publications: 5 publications found

Genes affected

CALM3 (HGNC:1449): (calmodulin 3) This gene encodes a member of a family of proteins that binds calcium and functions as a enzymatic co-factor. Activity of this protein is important in the regulation of the cell cycle and cytokinesis. Multiple alternatively spliced transcript variants have been observed at this gene. [provided by RefSeq, Aug 2016]

CALM3 Gene-Disease associations (from GenCC):

• familial long QT syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• long QT syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• long QT syndrome 16

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• catecholaminergic polymorphic ventricular tachycardia

  Inheritance: AD Classification: MODERATE Submitted by: G2P, ClinGen

LOC124904729 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 19-46608504-G-A is Benign according to our data. Variant chr19-46608504-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 240117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.93 with no splicing effect.
• BS2: High AC in GnomAd4 at 397 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005184.4. 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
	CALM3	NM_005184.4	MANE Select	c.201G>A	p.Pro67Pro	synonymous	Exon 4 of 6	NP_005175.2	P0DP25
	CALM3	NM_001329922.1		c.201G>A	p.Pro67Pro	synonymous	Exon 4 of 6	NP_001316851.1	P0DP23
	CALM3	NM_001329921.1		c.93G>A	p.Pro31Pro	synonymous	Exon 4 of 6	NP_001316850.1	Q96HY3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALM3	ENST00000291295.14	TSL:1 MANE Select	c.201G>A	p.Pro67Pro	synonymous	Exon 4 of 6	ENSP00000291295.8	P0DP25
	CALM3	ENST00000599839.5	TSL:1	c.93G>A	p.Pro31Pro	synonymous	Exon 5 of 7	ENSP00000471225.1	Q96HY3
	CALM3	ENST00000866718.1		c.201G>A	p.Pro67Pro	synonymous	Exon 4 of 6	ENSP00000536777.1

Frequencies

GnomAD3 genomes AF: 0.00262 AC: 398 AN: 152160 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000941

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00463

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00221 AC: 556 AN: 251480 AF XY: 0.00220

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00179

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.000693

Gnomad NFE exome AF: 0.00390

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00402 AC: 5880 AN: 1461782 Hom.: 24 Cov.: 31 AF XY: 0.00391 AC XY: 2843 AN XY: 727196

African (AFR) AF: 0.000478 AC: 16 AN: 33480

American (AMR) AF: 0.00181 AC: 81 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000536 AC: 14 AN: 26136

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.000749 AC: 40 AN: 53418

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00494 AC: 5492 AN: 1111906

Other (OTH) AF: 0.00376 AC: 227 AN: 60394

GnomAD4 genome AF: 0.00261 AC: 397 AN: 152278 Hom.: 3 Cov.: 32 AF XY: 0.00243 AC XY: 181 AN XY: 74458

African (AFR) AF: 0.000939 AC: 39 AN: 41554

American (AMR) AF: 0.00196 AC: 30 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00462 AC: 314 AN: 68012

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00334 Hom.: 1

Bravo AF: 0.00279

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00463

EpiControl AF: 0.00427

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	not provided (2)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Long QT syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.60
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs34089805; hg19: chr19-47111761;