Genetic Variant CALML6:p.Pro69Pro (chr1-1916569-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_138705.4(CALML6):c.207C>T(p.Pro69Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,611,726 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 5 hom. )

Consequence

CALML6
NM_138705.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.494

Publications

3 publications found

Variant links:

Genes affected

CALML6 (HGNC:24193): (calmodulin like 6) Predicted to enable calcium ion binding activity and enzyme regulator activity. Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CALML6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 1-1916569-C-T is Benign according to our data. Variant chr1-1916569-C-T is described in ClinVar as Benign. ClinVar VariationId is 781580.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138705.4. 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
	CALML6	NM_138705.4	MANE Select	c.207C>T	p.Pro69Pro	synonymous	Exon 3 of 6	NP_619650.2	Q8TD86
	CALML6	NM_001330313.2		c.156C>T	p.Pro52Pro	synonymous	Exon 2 of 5	NP_001317242.1	B1AKR1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CALML6	ENST00000307786.8	TSL:1 MANE Select	c.207C>T	p.Pro69Pro	synonymous	Exon 3 of 6	ENSP00000304643.3	Q8TD86
CALML6	ENST00000378604.3	TSL:3	c.156C>T	p.Pro52Pro	synonymous	Exon 2 of 5	ENSP00000367867.3	B1AKR1
CALML6	ENST00000482402.1	TSL:2	n.1304C>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.00138

AC:

209

AN:

151912

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.000662

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00144

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00177

AC:

440

AN:

248268

AF XY:

0.00192

show subpopulations

Gnomad AFR exome

AF:

0.0000624

Gnomad AMR exome

AF:

0.00114

Gnomad ASJ exome

AF:

0.0142

Gnomad EAS exome

AF:

0.0000546

Gnomad FIN exome

AF:

0.000372

Gnomad NFE exome

AF:

0.00166

Gnomad OTH exome

AF:

0.00331

GnomAD4 exome

AF:

0.00138

AC:

2011

AN:

1459694

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

1060

AN XY:

726046

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33388

American (AMR)

AF:

0.00115

AC:

AN:

44452

Ashkenazi Jewish (ASJ)

AF:

0.0145

AC:

376

AN:

26014

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00156

AC:

134

AN:

86014

European-Finnish (FIN)

AF:

0.000568

AC:

AN:

52838

Middle Eastern (MID)

AF:

0.00817

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00110

AC:

1220

AN:

1111270

Other (OTH)

AF:

0.00244

AC:

147

AN:

60292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

113

225

338

450

563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00137

AC:

209

AN:

152032

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

105

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.000410

AC:

AN:

41494

American (AMR)

AF:

0.00105

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0144

AC:

AN:

3472

East Asian (EAS)

AF:

0.000388

AC:

AN:

5154

South Asian (SAS)

AF:

0.00208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000662

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00144

AC:

AN:

67936

Other (OTH)

AF:

0.00332

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00230

Hom.:

Bravo

AF:

0.00134

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00256

EpiControl

AF:

0.00297

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

-0.49

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over