Genetic Variant CAPSL:p.Phe61Val (chr5-35910500-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001042625.2(CAPSL):c.181T>G(p.Phe61Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,612,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

CAPSL
NM_001042625.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.35

Publications

1 publications found

Variant links:

Genes affected

CAPSL (HGNC:28375): (calcyphosine like) Predicted to enable calcium ion binding activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CAPSL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08576617).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042625.2. 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
	CAPSL	NM_001042625.2	MANE Select	c.181T>G	p.Phe61Val	missense	Exon 3 of 5	NP_001036090.1	Q8WWF8
	CAPSL	NM_144647.4		c.181T>G	p.Phe61Val	missense	Exon 3 of 5	NP_653248.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CAPSL	ENST00000651391.1	MANE Select	c.181T>G	p.Phe61Val	missense	Exon 3 of 5	ENSP00000498465.1	Q8WWF8
CAPSL	ENST00000397367.6	TSL:1	c.181T>G	p.Phe61Val	missense	Exon 3 of 5	ENSP00000380524.2	Q8WWF8
CAPSL	ENST00000397366.5	TSL:3	c.181T>G	p.Phe61Val	missense	Exon 3 of 5	ENSP00000380523.1	Q8WWF8

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000280

AC:

AN:

250182

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000436

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1460046

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726328

show subpopulations

African (AFR)

AF:

0.000747

AC:

AN:

33448

American (AMR)

AF:

0.00

AC:

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39660

South Asian (SAS)

AF:

0.00

AC:

AN:

85922

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53354

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110854

Other (OTH)

AF:

0.0000332

AC:

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.428

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000230

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.000770

AC:

AN:

41566

American (AMR)

AF:

0.000131

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.0000988

Hom.:

Bravo

AF:

0.000306

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.37

Eigen

Benign

-0.11

Eigen_PC

Benign

0.049

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.84

M_CAP

Benign

0.044

MetaRNN

Benign

0.086

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.2

PhyloP100

2.4

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.16

Sift

Benign

0.37

Sift4G

Benign

0.49

Polyphen

0.0020

Vest4

0.34

MVP

0.69

MPC

0.020

ClinPred

0.080

GERP RS

5.3

Varity_R

0.49

gMVP

0.65

Mutation Taster

=67/33

polymorphism

(source)

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

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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