dbSNP rs41288626: ATP11A:c.334-6T>A (chr13-112810613-T-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_015205.3(ATP11A):c.334-6T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00707 in 1,612,874 control chromosomes in the GnomAD database, including 55 homozygotes. 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 0.0058 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0072 ( 51 hom. )

Consequence

ATP11A
NM_015205.3 splice_region, intron

Scores

Splicing: ADA: 0.00002776

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.295

Publications

2 publications found

Variant links:

Genes affected

ATP11A (HGNC:13552): (ATPase phospholipid transporting 11A) The protein encoded by this gene is an integral membrane ATPase. The encoded protein is probably phosphorylated in its intermediate state and likely drives the transport of ions such as calcium across membranes. [provided by RefSeq, Apr 2022]

ATP11A Gene-Disease associations (from GenCC):

auditory neuropathy, autosomal dominant 2
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
complex neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
hearing loss, autosomal dominant 84
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
leukodystrophy, hypomyelinating, 24
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ATP11A links:

ENSG00000303208 (HGNC:):

ENSG00000303208 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 13-112810613-T-A is Benign according to our data. Variant chr13-112810613-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 710232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 889 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015205.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATP11A	NM_015205.3	MANE Select	c.334-6T>A	splice_region intron	N/A	NP_056020.2	P98196
ATP11A	NM_001405661.1		c.334-6T>A	splice_region intron	N/A	NP_001392590.1
ATP11A	NM_032189.4		c.334-6T>A	splice_region intron	N/A	NP_115565.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATP11A	ENST00000375645.8	TSL:5 MANE Select	c.334-6T>A	splice_region intron	N/A	ENSP00000364796.3	P98196
ATP11A	ENST00000418678.5	TSL:1	c.256-6T>A	splice_region intron	N/A	ENSP00000396374.1	H0Y547
ATP11A	ENST00000375630.6	TSL:5	c.334-6T>A	splice_region intron	N/A	ENSP00000364781.2	E9PEJ6

Frequencies

GnomAD3 genomes

AF:

0.00584

AC:

889

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.0127

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00816

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00668

AC:

1676

AN:

250846

AF XY:

0.00657

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.00293

Gnomad ASJ exome

AF:

0.0145

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0129

Gnomad NFE exome

AF:

0.00898

Gnomad OTH exome

AF:

0.00751

GnomAD4 exome

AF:

0.00719

AC:

10506

AN:

1460588

Hom.:

Cov.:

AF XY:

0.00704

AC XY:

5113

AN XY:

726646

show subpopulations

African (AFR)

AF:

0.00126

AC:

AN:

33458

American (AMR)

AF:

0.00264

AC:

118

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0153

AC:

401

AN:

26126

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39694

South Asian (SAS)

AF:

0.00230

AC:

198

AN:

86214

European-Finnish (FIN)

AF:

0.0125

AC:

663

AN:

53232

Middle Eastern (MID)

AF:

0.0128

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00775

AC:

8607

AN:

1111038

Other (OTH)

AF:

0.00663

AC:

400

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

510

1021

1531

2042

2552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.00584

AC:

889

AN:

152286

Hom.:

Cov.:

AF XY:

0.00608

AC XY:

453

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00115

AC:

AN:

41562

American (AMR)

AF:

0.00412

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0150

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00166

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0127

AC:

135

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00816

AC:

555

AN:

68018

Other (OTH)

AF:

0.00426

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

133

178

222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00792

Hom.:

Bravo

AF:

0.00520

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00834

EpiControl

AF:

0.00794

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.17

(source)

DANN

Benign

0.42

PhyloP100

-0.29

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000028

dbscSNV1_RF

Benign

0.010

SpliceAI score (max)

0.010

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