Genetic Variant NM_001168221.2:c.5335C>T (chr2-201487740-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001168221.2(CATSPERT):c.5335C>T(p.Arg1779*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000533 in 1,614,012 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00080 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00050 ( 1 hom. )

Consequence

CATSPERT
NM_001168221.2 stop_gained

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.557

Publications

8 publications found

Variant links:

Genes affected

CATSPERT (HGNC:14438): (C2 calcium dependent domain containing 6) An autosomal recessive form of juvenile amyotrophic lateral sclerosis was originally mapped to a region of chromosome 2 that includes this gene. The encoded protein contains a calcium-dependent membrane targeting C2 domain. This domain is often found in proteins that are involved in membrane trafficking and signal transduction. [provided by RefSeq, Jun 2016]

CATSPERT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001168221.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CATSPERT	NM_001168221.2	MANE Select	c.5335C>T	p.Arg1779*	stop_gained	Exon 16 of 16	NP_001161693.1	Q53TS8-4
CATSPERT	NM_152525.6		c.1744C>T	p.Arg582*	stop_gained	Exon 15 of 15	NP_689738.3
CATSPERT	NM_001168216.2		c.*212C>T		3_prime_UTR	Exon 13 of 13	NP_001161688.1	Q53TS8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C2CD6	ENST00000439140.6	TSL:1 MANE Select	c.5335C>T	p.Arg1779*	stop_gained	Exon 16 of 16	ENSP00000409937.1	Q53TS8-4
C2CD6	ENST00000286195.7	TSL:1	c.1744C>T	p.Arg582*	stop_gained	Exon 15 of 15	ENSP00000286195.3	Q53TS8-1
C2CD6	ENST00000957096.1		c.4912C>T	p.Arg1638*	stop_gained	Exon 13 of 13	ENSP00000627155.1

Frequencies

GnomAD3 genomes

AF:

0.000809

AC:

123

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.000720

AC:

181

AN:

251452

AF XY:

0.000655

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00214

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000554

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.000505

AC:

738

AN:

1461850

Hom.:

Cov.:

AF XY:

0.000488

AC XY:

355

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.000209

AC:

AN:

33480

American (AMR)

AF:

0.00197

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00272

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39682

South Asian (SAS)

AF:

0.000336

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00364

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000417

AC:

464

AN:

1111994

Other (OTH)

AF:

0.000927

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

149

198

248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000802

AC:

122

AN:

152162

Hom.:

Cov.:

AF XY:

0.000860

AC XY:

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41506

American (AMR)

AF:

0.00223

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000676

AC:

AN:

68006

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.000792

Hom.:

Bravo

AF:

0.00103

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000568

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Spermatogenic failure 68 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

0.0057

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

(source)

DANN

Benign

0.94

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.026

PhyloP100

0.56

Vest4

0.20

GERP RS

0.78

Mutation Taster

=155/45

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

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