dbSNP rs199568379: ATP12A:p.Asn144Asn (chr13-24688522-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001676.7(ATP12A):c.432C>T(p.Asn144Asn) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,577,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

ATP12A
NM_001676.7 splice_region, synonymous

Scores

Splicing: ADA: 0.0001053

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.52

Publications

2 publications found

Variant links:

Genes affected

ATP12A (HGNC:13816): (ATPase H+/K+ transporting non-gastric alpha2 subunit) The protein encoded by this gene belongs to the family of P-type cation transport ATPases. This gene encodes a catalytic subunit of the ouabain-sensitive H+/K+ -ATPase that catalyzes the hydrolysis of ATP coupled with the exchange of H(+) and K(+) ions across the plasma membrane. It is also responsible for potassium absorption in various tissues. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

ATP12A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 13-24688522-C-T is Benign according to our data. Variant chr13-24688522-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2643693.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.52 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001676.7. 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
	ATP12A	NM_001676.7	MANE Select	c.432C>T	p.Asn144Asn	splice_region synonymous	Exon 4 of 23	NP_001667.4
	ATP12A	NM_001185085.2		c.432C>T	p.Asn144Asn	splice_region synonymous	Exon 4 of 23	NP_001172014.1	P54707-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP12A	ENST00000381946.5	TSL:1 MANE Select	c.432C>T	p.Asn144Asn	splice_region synonymous	Exon 4 of 23	ENSP00000371372.3	P54707-1
ATP12A	ENST00000218548.10	TSL:1	c.432C>T	p.Asn144Asn	splice_region synonymous	Exon 4 of 23	ENSP00000218548.6	P54707-2
ATP12A	ENST00000911814.1		c.229-740C>T		intron	N/A	ENSP00000581873.1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000253

AC:

AN:

225164

AF XY:

0.000257

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000635

Gnomad ASJ exome

AF:

0.000896

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000690

Gnomad NFE exome

AF:

0.000313

Gnomad OTH exome

AF:

0.000186

GnomAD4 exome

AF:

0.000152

AC:

216

AN:

1424728

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

703838

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32614

American (AMR)

AF:

0.0000714

AC:

AN:

41998

Ashkenazi Jewish (ASJ)

AF:

0.00104

AC:

AN:

24100

East Asian (EAS)

AF:

0.00

AC:

AN:

39012

South Asian (SAS)

AF:

0.0000501

AC:

AN:

79764

European-Finnish (FIN)

AF:

0.000688

AC:

AN:

52362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5600

European-Non Finnish (NFE)

AF:

0.000129

AC:

141

AN:

1090582

Other (OTH)

AF:

0.000119

AC:

AN:

58696

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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:

0.000210

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41580

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.000233

Hom.:

Bravo

AF:

0.000106

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely 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

-0.80

CADD

Benign

0.13

(source)

DANN

Benign

0.66

PhyloP100

-1.5

Mutation Taster

=77/23

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.052

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

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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