chr13-112690429-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015205.3(ATP11A):c.13C>T(p.Leu5Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 1,346,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

ATP11A
NM_015205.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.847

Publications

1 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:

ENSG00000274922 (HGNC:):

ENSG00000274922 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08272624).

BS2

High AC in GnomAdExome4 at 9 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	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP11A	NM_015205.3	MANE Select	c.13C>T	p.Leu5Phe	missense	Exon 1 of 30	NP_056020.2	P98196
ATP11A	NM_001405661.1		c.13C>T	p.Leu5Phe	missense	Exon 1 of 29	NP_001392590.1
ATP11A	NM_032189.4		c.13C>T	p.Leu5Phe	missense	Exon 1 of 29	NP_115565.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP11A	ENST00000375645.8	TSL:5 MANE Select	c.13C>T	p.Leu5Phe	missense	Exon 1 of 30	ENSP00000364796.3	P98196
ATP11A	ENST00000375630.6	TSL:5	c.13C>T	p.Leu5Phe	missense	Exon 1 of 29	ENSP00000364781.2	E9PEJ6
ATP11A	ENST00000487903.5	TSL:5	c.13C>T	p.Leu5Phe	missense	Exon 1 of 30	ENSP00000420387.1	P98196

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151770

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

GnomAD2 exomes

AF:

0.0000135

AC:

AN:

74254

AF XY:

0.0000233

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000753

AC:

AN:

1194490

Hom.:

Cov.:

AF XY:

0.00000860

AC XY:

AN XY:

581614

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25624

American (AMR)

AF:

0.000246

AC:

AN:

16232

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17690

East Asian (EAS)

AF:

0.00

AC:

AN:

29756

South Asian (SAS)

AF:

0.0000227

AC:

AN:

43980

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31066

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3710

European-Non Finnish (NFE)

AF:

0.00000409

AC:

AN:

978564

Other (OTH)

AF:

0.00

AC:

AN:

47868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

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:

0.00000659

AC:

AN:

151770

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74128

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41396

American (AMR)

AF:

0.0000655

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10470

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67882

Other (OTH)

AF:

0.00

AC:

AN:

2088

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000178

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.65

M_CAP

Pathogenic

0.60

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

0.85

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.44

REVEL

Benign

0.16

Sift

Benign

0.039

Sift4G

Benign

0.75

Polyphen

0.0

Vest4

0.18

MutPred

0.55

Gain of catalytic residue at M1 (P = 0)

MVP

0.20

MPC

0.32

ClinPred

0.058

GERP RS

2.5

PromoterAI

0.0014

Neutral

(source)

Varity_R

0.076

gMVP

0.51

Mutation Taster

=85/15

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over