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

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 id is 781580.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALML6	NM_138705.4 link	c.207C>T	p.Pro69Pro	synonymous_variant	Exon 3 of 6	ENST00000307786.8	NP_619650.2	Q8TD86
CALML6	NM_001330313.2 link	c.156C>T	p.Pro52Pro	synonymous_variant	Exon 2 of 5		NP_001317242.1	B1AKR1
CALML6	XM_005244729.4 link	c.273C>T	p.Pro91Pro	synonymous_variant	Exon 3 of 6		XP_005244786.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CALML6	ENST00000307786.8 link	c.207C>T	p.Pro69Pro	synonymous_variant	Exon 3 of 6	1	NM_138705.4	ENSP00000304643.3	Q8TD86
CALML6	ENST00000378604.3 link	c.156C>T	p.Pro52Pro	synonymous_variant	Exon 2 of 5	3		ENSP00000367867.3	B1AKR1
CALML6	ENST00000482402.1 link	n.1304C>T		non_coding_transcript_exon_variant	Exon 1 of 3	2
CALML6	ENST00000462293.1 link	n.328-183C>T		intron_variant	Intron 1 of 2	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

Gnomad4 AFR exome

AF:

0.000180

AC:

AN:

33388

Gnomad4 AMR exome

AF:

0.00115

AC:

AN:

44452

Gnomad4 ASJ exome

AF:

0.0145

AC:

376

AN:

26014

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39670

Gnomad4 SAS exome

AF:

0.00156

AC:

134

AN:

86014

Gnomad4 FIN exome

AF:

0.000568

AC:

AN:

52838

Gnomad4 NFE exome

AF:

0.00110

AC:

1220

AN:

1111270

Gnomad4 Remaining exome

AF:

0.00244

AC:

147

AN:

60292

Heterozygous variant carriers

113

225

338

450

563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Gnomad4 AFR

AF:

0.000410

AC:

0.000409698

AN:

0.000409698

Gnomad4 AMR

AF:

0.00105

AC:

0.00104739

AN:

0.00104739

Gnomad4 ASJ

AF:

0.0144

AC:

0.0144009

AN:

0.0144009

Gnomad4 EAS

AF:

0.000388

AC:

0.000388048

AN:

0.000388048

Gnomad4 SAS

AF:

0.00208

AC:

0.00207641

AN:

0.00207641

Gnomad4 FIN

AF:

0.000662

AC:

0.000662252

AN:

0.000662252

Gnomad4 NFE

AF:

0.00144

AC:

0.00144253

AN:

0.00144253

Gnomad4 OTH

AF:

0.00332

AC:

0.00331754

AN:

0.00331754

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 24, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.89

Mutation Taster

=97/3

polymorphism

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over